Protocol Index	

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OP RESEARCH PRO00033015 ONC-392-001 CHANG	

Types:      Research Oncology Treatment
Synonyms:  ADVANCED, SOLID, TUMORS, NSCLC

Cycle 1	Repeat 1 time	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	ONC INFUSION APPOINTMENT REQUEST 8	Interval: --	Occurrences: --			Line Flush
  	sodium chloride 0.9% flush 25 mL	Dose: 25 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Please refer to Protocol Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: see 1.10.3 Study Schedule in Part C: Table 4: Study Schedule for Expansion Cohorts Part C Arm B. see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
		  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	Please refer to Section 7.9 Immune-mediated Adverse Reaction (IMAR) Management Plan and Table 12: Dose Modifications for IMARS: see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
		  	ONC NURSING COMMUNICATION 6	Interval: --	Occurrences: --	Comments:	Please refer to Protocol Section 7.10 Prophylactic and Acute Management of Infusion Reactions: Prophylaxis Pre-Medications, Post-Infusion Management, and Treatment Recommendations for Grade 1, 2, 3, 4 Symptoms  see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Taken within 20 minutes pre-infusion, within 30 minutes post infusion completion, and 2 hours post infusion completion (±15 minutes).
		  	MEASURE WEIGHT	Interval: --	Occurrences: --		  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	Physical Exam + ECOG
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	ABSOLUTE NEUTROPHIL COUNT	Interval: --	Occurrences: --		  	ABSOLUTE LYMPHOCYTE COUNT	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --			Labs
  	BILIRUBIN DIRECT	Interval: --	Occurrences: --			Labs
  	LDH	Interval: --	Occurrences: --			Labs
  	THYROID STIMULATING HORMONE	Interval: --	Occurrences: --		  	T3	Interval: --	Occurrences: --		  	T4, FREE	Interval: --	Occurrences: --			Labs
  	CANCER ANTIGEN 125	Interval: --	Occurrences: --		  	CANCER ANTIGEN 15-3	Interval: --	Occurrences: --		  	MISCELLANEOUS REFERRAL TEST	Interval: --	Occurrences: --	Comments:	Cancer antigen 27-29 (CA-BR)
		  	CARCINOEMBRYONIC ANTIGEN (CEA)	Interval: --	Occurrences: --			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Pre-Medications
  	acetaminophen (TYLENOL) tablet 487.5 mg	Dose: 500 mg	Route: oral	once for 1 dose	Start: S			Instructions:	30 minutes prior to first infusion of the cycle.		  	diphenhydrAMINE (BENADRYL) tablet 25 mg	Dose: 25 mg	Route: oral	once for 1 dose	Start: S			Instructions:	Dose = 25-50 mg 30 minutes prior to first infusion of the cycle.		  	famotidine (PEPCID) tablet 20 mg	Dose: 20 mg	Route: oral	once for 1 dose	Start: S			Instructions:	30 minutes prior to first infusion of the cycle.		  	hydrocortisone sodium succinate (Solu-CORTEF) injection 50 mg	Dose: 50 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Either IV or PO. 30 minutes prior to first infusion of the cycle.			Nursing Orders
  	TREATMENT CONDITIONS 13	Interval: --	Occurrences: --	Comments:	HOLD and notify provider if 
o ANC LESS than 1000; 
o Platelets LESS than 100,000; 
o AST or ALT GREATER than 3 times ULN or total bilirubin GREATER than 1.5 times ULN; 
o Serum creatinine GREATER than 1.5x ULN or 1.5x ABOVE baseline.
			Provider Communication
  	ONC PROVIDER COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Dose adjustment allowed: 
Level 1: 6 mg/kg; 
Level 2: 3 mg/kg; 
Adjustment from 10 to 3 mg/kg is allowed. 
			Chemotherapy
  	INV-ONC-392 (ONC-392-001/Pro00033015/Chang) 10 mg/kg in dextrose 5% 500 mL	Dose: 10 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose			Offset: 30 Minutes	Instructions:	Administer intravenously using 0.2 micron inline filter over 90 minutes for initial infusion, then over 60 minutes for subsequent infusions. After the infusion, flush by adding 25mL of 0.9% NaCl to the IV bag to ensure all drug is infused. Prepared bag/syringe is stable for 4 hours at room temperature. 
Final concentration can be between 0.5mg/mL to 3mg/mL. 
HAZARDOUS - Handle with care
Caution: New Drug-Limited by Federal (USA) Law to Investigational use.

	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ONC-392 30 MG/ML INTRAVENOUS SOLN (ONC-392-001/PRO00033015/CHANG)	Medications	10 mg/kg	Main Ingredient	Yes	DEXTROSE 5 % IN WATER (D5W) INTRAVENOUS SOLUTION	QS Base	500 mL	Yes	Yes				Post-Hydration
  	sodium chloride 0.9 % infusion	Dose: --	Route: intravenous	continuous	Start: S					Nursing Orders
  	ONC NURSING COMMUNICATION 11	Interval: --	Occurrences: --	Comments:	Post-infusion observation time is minimum 2 hours (±15 minutes)
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
6. Notify the treating physician.
7. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
8. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain) 
1. Stop the infusion. 
2. Notify the CERT team and treating physician immediately. 
3. Place the patient on continuous monitoring. 
4. Obtain vital signs. 
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%. 
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing. 
7. Administer diphenhydramine 50 mg intravenous once and acetaminophen 650 mg once. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg  orally and Famotidine 20 mg intravenous once. 
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe). 
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician. 
10. If the infusion is interrupted, then restart the infusion at 50% of the original infusion rate when symptoms resolve.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 - SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise - cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg,  confusion, collapse, loss of consciousness, or incontinence) 
1. Stop the infusion. 
2. Notify the CERT team and treating physician immediately. 
3. Place the patient on continuous monitoring. 
4. Obtain vital signs. 
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position. 
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%. 
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing. 
8. Administer diphenhydramine 50 mg intravenous once and methylprednisolone 100 mg. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg  orally and Famotidine 20 mg intravenous once. 
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous. 
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 8	Interval: --	Occurrences: --	Comments:	Grade 4 Infusion Reaction: life-threatening; pressor or ventilator support indicated. See Emergency Medications. 
		  	ONC NURSING COMMUNICATION 9	Interval: --	Occurrences: --	Comments:	Treatment and safety management decisions all to be based upon local laboratory data.  Protocol does not provide reference ranges.
		  	sodium chloride 0.9 % infusion	Dose: 50-100 mL/hr	Route: intravenous	PRN	Start: S				  	sodium chloride 0.9 % infusion	Dose: 1,000 mL	Route: intravenous	PRN	Start: S				  	acetaminophen (TYLENOL) tablet 650 mg	Dose: 650 mg	Route: oral	PRN	Start: S				  	diphenhydrAMINE (BENADRYL) injection 50 mg	Dose: 50 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	methylPREDNISolone sodium succinate (Solu-MEDROL) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN	Start: S				  	epINEPHrine (ADRENALIN) injection 1 mg/mL 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 2	Repeat 1 time	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	ONC INFUSION APPOINTMENT REQUEST 5	Interval: --	Occurrences: --			Line Flush
  	sodium chloride 0.9% flush 25 mL	Dose: 25 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Please refer to Protocol Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: see 1.10.3 Study Schedule in Part C: Table 4: Study Schedule for Expansion Cohorts Part C Arm B. see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
		  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	Please refer to Section 7.9 Immune-mediated Adverse Reaction (IMAR) Management Plan and Table 12: Dose Modifications for IMARS: see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
		  	ONC NURSING COMMUNICATION 6	Interval: --	Occurrences: --	Comments:	Please refer to Protocol Section 7.10 Prophylactic and Acute Management of Infusion Reactions: Prophylaxis Pre-Medications, Post-Infusion Management, and Treatment Recommendations for Grade 1, 2, 3, 4 Symptoms  see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Taken within 20 minutes pre-infusion and 30 (±10) minutes of infusion completion
		  	MEASURE WEIGHT	Interval: --	Occurrences: --		  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	Physical Exam + ECOG
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	ABSOLUTE NEUTROPHIL COUNT	Interval: --	Occurrences: --		  	ABSOLUTE LYMPHOCYTE COUNT	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --			Labs
  	BILIRUBIN DIRECT	Interval: --	Occurrences: --			Labs
  	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --			Labs
  	CANCER ANTIGEN 125	Interval: --	Occurrences: --		  	CANCER ANTIGEN 15-3	Interval: --	Occurrences: --		  	MISCELLANEOUS REFERRAL TEST	Interval: --	Occurrences: --	Comments:	Cancer antigen 27-29 (CA-BR)
		  	CARCINOEMBRYONIC ANTIGEN (CEA)	Interval: --	Occurrences: --			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Nursing Orders
  	TREATMENT CONDITIONS 13	Interval: --	Occurrences: --	Comments:	HOLD and notify provider if 
o ANC LESS than 1000; 
o Platelets LESS than 100,000; 
o AST or ALT GREATER than 3 times ULN or total bilirubin GREATER than 1.5 times ULN; 
o Serum creatinine GREATER than 1.5x ULN or 1.5x ABOVE baseline.
			Provider Communication
  	ONC PROVIDER COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Dose adjustment allowed: 
Level 1: 6 mg/kg; 
Level 2: 3 mg/kg; 
Adjustment from 10 to 3 mg/kg is allowed. 
			Chemotherapy
  	INV-ONC-392 (ONC-392-001/Pro00033015/Chang) 10 mg/kg in dextrose 5% 500 mL	Dose: 10 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose			Offset: 30 Minutes	Instructions:	Administer intravenously using 0.2 micron inline filter over 90 minutes for initial infusion, then over 60 minutes for subsequent infusions. After the infusion, flush by adding 25mL of 0.9% NaCl to the IV bag to ensure all drug is infused. Prepared bag/syringe is stable for 4 hours at room temperature. 
Final concentration can be between 0.5mg/mL to 3mg/mL. 
HAZARDOUS - Handle with care
Caution: New Drug-Limited by Federal (USA) Law to Investigational use.

	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ONC-392 30 MG/ML INTRAVENOUS SOLN (ONC-392-001/PRO00033015/CHANG)	Medications	10 mg/kg	Main Ingredient	Yes	DEXTROSE 5 % IN WATER (D5W) INTRAVENOUS SOLUTION	QS Base	500 mL	Yes	Yes				Post-Hydration
  	sodium chloride 0.9 % infusion	Dose: --	Route: intravenous	continuous	Start: S					Nursing Orders
  	ONC NURSING COMMUNICATION 11	Interval: --	Occurrences: --	Comments:	Post-infusion observation time is minimum 2 hours (±15 minutes)
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
6. Notify the treating physician.
7. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
8. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain) 
1. Stop the infusion. 
2. Notify the CERT team and treating physician immediately. 
3. Place the patient on continuous monitoring. 
4. Obtain vital signs. 
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%. 
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing. 
7. Administer diphenhydramine 50 mg intravenous once and acetaminophen 650 mg once. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg  orally and Famotidine 20 mg intravenous once. 
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe). 
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician. 
10. If the infusion is interrupted, then restart the infusion at 50% of the original infusion rate when symptoms resolve.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 - SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise - cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg,  confusion, collapse, loss of consciousness, or incontinence) 
1. Stop the infusion. 
2. Notify the CERT team and treating physician immediately. 
3. Place the patient on continuous monitoring. 
4. Obtain vital signs. 
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position. 
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%. 
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing. 
8. Administer diphenhydramine 50 mg intravenous once and methylprednisolone 100 mg. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg  orally and Famotidine 20 mg intravenous once. 
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous. 
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 8	Interval: --	Occurrences: --	Comments:	Grade 4 Infusion Reaction: life-threatening; pressor or ventilator support indicated. See Emergency Medications. 
		  	ONC NURSING COMMUNICATION 9	Interval: --	Occurrences: --	Comments:	Treatment and safety management decisions all to be based upon local laboratory data.  Protocol does not provide reference ranges.
		  	sodium chloride 0.9 % infusion	Dose: 50-100 mL/hr	Route: intravenous	PRN	Start: S				  	sodium chloride 0.9 % infusion	Dose: 1,000 mL	Route: intravenous	PRN	Start: S				  	acetaminophen (TYLENOL) tablet 650 mg	Dose: 650 mg	Route: oral	PRN	Start: S				  	diphenhydrAMINE (BENADRYL) injection 50 mg	Dose: 50 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	methylPREDNISolone sodium succinate (Solu-MEDROL) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN	Start: S				  	epINEPHrine (ADRENALIN) injection 1 mg/mL 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 3	Repeat 1 time	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	ONC INFUSION APPOINTMENT REQUEST 5	Interval: --	Occurrences: --			Line Flush
  	sodium chloride 0.9% flush 25 mL	Dose: 25 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Please refer to Protocol Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: see 1.10.3 Study Schedule in Part C: Table 4: Study Schedule for Expansion Cohorts Part C Arm B. see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
		  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	Please refer to Section 7.9 Immune-mediated Adverse Reaction (IMAR) Management Plan and Table 12: Dose Modifications for IMARS: see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
		  	ONC NURSING COMMUNICATION 6	Interval: --	Occurrences: --	Comments:	Please refer to Protocol Section 7.10 Prophylactic and Acute Management of Infusion Reactions: Prophylaxis Pre-Medications, Post-Infusion Management, and Treatment Recommendations for Grade 1, 2, 3, 4 Symptoms  see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Taken within 20 minutes pre-infusion and 30 (±10) minutes of infusion completion
		  	MEASURE WEIGHT	Interval: --	Occurrences: --		  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	Physical Exam + ECOG
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	ABSOLUTE NEUTROPHIL COUNT	Interval: --	Occurrences: --		  	ABSOLUTE LYMPHOCYTE COUNT	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --			Labs
  	BILIRUBIN DIRECT	Interval: --	Occurrences: --			Labs
  	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --			Labs
  	CANCER ANTIGEN 125	Interval: --	Occurrences: --		  	CANCER ANTIGEN 15-3	Interval: --	Occurrences: --		  	MISCELLANEOUS REFERRAL TEST	Interval: --	Occurrences: --	Comments:	Cancer antigen 27-29 (CA-BR)
		  	CARCINOEMBRYONIC ANTIGEN (CEA)	Interval: --	Occurrences: --			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Fresh Tumor Biopsies at Screening and once after cycle 3. Requires additional consent. Please order if appropriate.
			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Nursing Orders
  	TREATMENT CONDITIONS 13	Interval: --	Occurrences: --	Comments:	HOLD and notify provider if 
o ANC LESS than 1000; 
o Platelets LESS than 100,000; 
o AST or ALT GREATER than 3 times ULN or total bilirubin GREATER than 1.5 times ULN; 
o Serum creatinine GREATER than 1.5x ULN or 1.5x ABOVE baseline.
			Provider Communication
  	ONC PROVIDER COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Dose adjustment allowed: 
Level 1: 6 mg/kg; 
Level 2: 3 mg/kg; 
Adjustment from 10 to 3 mg/kg is allowed. 
			Chemotherapy
  	INV-ONC-392 (ONC-392-001/Pro00033015/Chang) 6 mg/kg in dextrose 5% 500 mL	Dose: 6 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose			Offset: 30 Minutes	Instructions:	Administer intravenously using 0.2 micron inline filter over 90 minutes for initial infusion, then over 60 minutes for subsequent infusions. After the infusion, flush by adding 25mL of 0.9% NaCl to the IV bag to ensure all drug is infused. Prepared bag/syringe is stable for 4 hours at room temperature. 
Final concentration can be between 0.5mg/mL to 3mg/mL. 
HAZARDOUS - Handle with care
Caution: New Drug-Limited by Federal (USA) Law to Investigational use.

	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ONC-392 30 MG/ML INTRAVENOUS SOLN (ONC-392-001/PRO00033015/CHANG)	Medications	6 mg/kg	Main Ingredient	Yes	DEXTROSE 5 % IN WATER (D5W) INTRAVENOUS SOLUTION	QS Base	500 mL	Yes	Yes				Post-Hydration
  	sodium chloride 0.9 % infusion	Dose: --	Route: intravenous	continuous	Start: S					Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Post-infusion observation time is minimum 30 minutes (±10 minutes)
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
6. Notify the treating physician.
7. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
8. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain) 
1. Stop the infusion. 
2. Notify the CERT team and treating physician immediately. 
3. Place the patient on continuous monitoring. 
4. Obtain vital signs. 
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%. 
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing. 
7. Administer diphenhydramine 50 mg intravenous once and acetaminophen 650 mg once. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg  orally and Famotidine 20 mg intravenous once. 
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe). 
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician. 
10. If the infusion is interrupted, then restart the infusion at 50% of the original infusion rate when symptoms resolve.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 - SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise - cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg,  confusion, collapse, loss of consciousness, or incontinence) 
1. Stop the infusion. 
2. Notify the CERT team and treating physician immediately. 
3. Place the patient on continuous monitoring. 
4. Obtain vital signs. 
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position. 
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%. 
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing. 
8. Administer diphenhydramine 50 mg intravenous once and methylprednisolone 100 mg. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg  orally and Famotidine 20 mg intravenous once. 
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous. 
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 8	Interval: --	Occurrences: --	Comments:	Grade 4 Infusion Reaction: life-threatening; pressor or ventilator support indicated. See Emergency Medications. 
		  	ONC NURSING COMMUNICATION 9	Interval: --	Occurrences: --	Comments:	Treatment and safety management decisions all to be based upon local laboratory data.  Protocol does not provide reference ranges.
		  	sodium chloride 0.9 % infusion	Dose: 50-100 mL/hr	Route: intravenous	PRN	Start: S				  	sodium chloride 0.9 % infusion	Dose: 1,000 mL	Route: intravenous	PRN	Start: S				  	acetaminophen (TYLENOL) tablet 650 mg	Dose: 650 mg	Route: oral	PRN	Start: S				  	diphenhydrAMINE (BENADRYL) injection 50 mg	Dose: 50 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	methylPREDNISolone sodium succinate (Solu-MEDROL) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN	Start: S				  	epINEPHrine (ADRENALIN) injection 1 mg/mL 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled				Day 8	Perform every 1 day x1		Imaging
  	CT CHEST W CONTRAST ABDOMEN W CONTRAST PELVIS W CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI with preference for CT. If MRI is needed, please order as appropriate.
					
Cycle 4	Repeat 1 time	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	ONC INFUSION APPOINTMENT REQUEST 5	Interval: --	Occurrences: --			Line Flush
  	sodium chloride 0.9% flush 25 mL	Dose: 25 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Please refer to Protocol Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: see 1.10.3 Study Schedule in Part C: Table 4: Study Schedule for Expansion Cohorts Part C Arm B. see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
		  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	Please refer to Section 7.9 Immune-mediated Adverse Reaction (IMAR) Management Plan and Table 12: Dose Modifications for IMARS: see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
		  	ONC NURSING COMMUNICATION 6	Interval: --	Occurrences: --	Comments:	Please refer to Protocol Section 7.10 Prophylactic and Acute Management of Infusion Reactions: Prophylaxis Pre-Medications, Post-Infusion Management, and Treatment Recommendations for Grade 1, 2, 3, 4 Symptoms  see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Taken within 20 minutes pre-infusion and 30 (±10) minutes of infusion completion
		  	MEASURE WEIGHT	Interval: --	Occurrences: --		  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	Physical Exam + ECOG
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	ABSOLUTE NEUTROPHIL COUNT	Interval: --	Occurrences: --		  	ABSOLUTE LYMPHOCYTE COUNT	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --			Labs
  	BILIRUBIN DIRECT	Interval: --	Occurrences: --			Labs
  	LDH	Interval: --	Occurrences: --			Labs
  	THYROID STIMULATING HORMONE	Interval: --	Occurrences: --		  	T3	Interval: --	Occurrences: --		  	T4, FREE	Interval: --	Occurrences: --			Labs
  	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --			Labs
  	CANCER ANTIGEN 125	Interval: --	Occurrences: --		  	CANCER ANTIGEN 15-3	Interval: --	Occurrences: --		  	MISCELLANEOUS REFERRAL TEST	Interval: --	Occurrences: --	Comments:	Cancer antigen 27-29 (CA-BR)
		  	CARCINOEMBRYONIC ANTIGEN (CEA)	Interval: --	Occurrences: --			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Nursing Orders
  	TREATMENT CONDITIONS 13	Interval: --	Occurrences: --	Comments:	HOLD and notify provider if 
o ANC LESS than 1000; 
o Platelets LESS than 100,000; 
o AST or ALT GREATER than 3 times ULN or total bilirubin GREATER than 1.5 times ULN; 
o Serum creatinine GREATER than 1.5x ULN or 1.5x ABOVE baseline.
			Provider Communication
  	ONC PROVIDER COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Dose adjustment allowed: 
Level 1: 6 mg/kg; 
Level 2: 3 mg/kg; 
Adjustment from 10 to 3 mg/kg is allowed. 
			Chemotherapy
  	INV-ONC-392 (ONC-392-001/Pro00033015/Chang) 6 mg/kg in dextrose 5% 500 mL	Dose: 6 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose			Offset: 30 Minutes	Instructions:	Administer intravenously using 0.2 micron inline filter over 90 minutes for initial infusion, then over 60 minutes for subsequent infusions. After the infusion, flush by adding 25mL of 0.9% NaCl to the IV bag to ensure all drug is infused. Prepared bag/syringe is stable for 4 hours at room temperature. 
Final concentration can be between 0.5mg/mL to 3mg/mL. 
HAZARDOUS - Handle with care
Caution: New Drug-Limited by Federal (USA) Law to Investigational use.

	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ONC-392 30 MG/ML INTRAVENOUS SOLN (ONC-392-001/PRO00033015/CHANG)	Medications	6 mg/kg	Main Ingredient	Yes	DEXTROSE 5 % IN WATER (D5W) INTRAVENOUS SOLUTION	QS Base	500 mL	Yes	Yes				Post-Hydration
  	sodium chloride 0.9 % infusion	Dose: --	Route: intravenous	continuous	Start: S					Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Post-infusion observation time is minimum 30 minutes (±10 minutes)
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
6. Notify the treating physician.
7. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
8. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain) 
1. Stop the infusion. 
2. Notify the CERT team and treating physician immediately. 
3. Place the patient on continuous monitoring. 
4. Obtain vital signs. 
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%. 
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing. 
7. Administer diphenhydramine 50 mg intravenous once and acetaminophen 650 mg once. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg  orally and Famotidine 20 mg intravenous once. 
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe). 
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician. 
10. If the infusion is interrupted, then restart the infusion at 50% of the original infusion rate when symptoms resolve.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 - SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise - cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg,  confusion, collapse, loss of consciousness, or incontinence) 
1. Stop the infusion. 
2. Notify the CERT team and treating physician immediately. 
3. Place the patient on continuous monitoring. 
4. Obtain vital signs. 
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position. 
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%. 
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing. 
8. Administer diphenhydramine 50 mg intravenous once and methylprednisolone 100 mg. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg  orally and Famotidine 20 mg intravenous once. 
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous. 
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 8	Interval: --	Occurrences: --	Comments:	Grade 4 Infusion Reaction: life-threatening; pressor or ventilator support indicated. See Emergency Medications. 
		  	ONC NURSING COMMUNICATION 9	Interval: --	Occurrences: --	Comments:	Treatment and safety management decisions all to be based upon local laboratory data.  Protocol does not provide reference ranges.
		  	sodium chloride 0.9 % infusion	Dose: 50-100 mL/hr	Route: intravenous	PRN	Start: S				  	sodium chloride 0.9 % infusion	Dose: 1,000 mL	Route: intravenous	PRN	Start: S				  	acetaminophen (TYLENOL) tablet 650 mg	Dose: 650 mg	Route: oral	PRN	Start: S				  	diphenhydrAMINE (BENADRYL) injection 50 mg	Dose: 50 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	methylPREDNISolone sodium succinate (Solu-MEDROL) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN	Start: S				  	epINEPHrine (ADRENALIN) injection 1 mg/mL 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 5	Repeat 1 time	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	ONC INFUSION APPOINTMENT REQUEST 5	Interval: --	Occurrences: --			Line Flush
  	sodium chloride 0.9% flush 25 mL	Dose: 25 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Please refer to Protocol Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: see 1.10.3 Study Schedule in Part C: Table 4: Study Schedule for Expansion Cohorts Part C Arm B. see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
		  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	Please refer to Section 7.9 Immune-mediated Adverse Reaction (IMAR) Management Plan and Table 12: Dose Modifications for IMARS: see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
		  	ONC NURSING COMMUNICATION 6	Interval: --	Occurrences: --	Comments:	Please refer to Protocol Section 7.10 Prophylactic and Acute Management of Infusion Reactions: Prophylaxis Pre-Medications, Post-Infusion Management, and Treatment Recommendations for Grade 1, 2, 3, 4 Symptoms  see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Taken within 20 minutes pre-infusion and 30 (±10) minutes of infusion completion
		  	MEASURE WEIGHT	Interval: --	Occurrences: --		  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	Physical Exam + ECOG
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	ABSOLUTE NEUTROPHIL COUNT	Interval: --	Occurrences: --		  	ABSOLUTE LYMPHOCYTE COUNT	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --			Labs
  	BILIRUBIN DIRECT	Interval: --	Occurrences: --			Labs
  	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --			Labs
  	CANCER ANTIGEN 125	Interval: --	Occurrences: --		  	CANCER ANTIGEN 15-3	Interval: --	Occurrences: --		  	MISCELLANEOUS REFERRAL TEST	Interval: --	Occurrences: --	Comments:	Cancer antigen 27-29 (CA-BR)
		  	CARCINOEMBRYONIC ANTIGEN (CEA)	Interval: --	Occurrences: --			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Nursing Orders
  	TREATMENT CONDITIONS 13	Interval: --	Occurrences: --	Comments:	HOLD and notify provider if 
o ANC LESS than 1000; 
o Platelets LESS than 100,000; 
o AST or ALT GREATER than 3 times ULN or total bilirubin GREATER than 1.5 times ULN; 
o Serum creatinine GREATER than 1.5x ULN or 1.5x ABOVE baseline.
			Provider Communication
  	ONC PROVIDER COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Dose adjustment allowed: 
Level 1: 6 mg/kg; 
Level 2: 3 mg/kg; 
Adjustment from 10 to 3 mg/kg is allowed. 
			Chemotherapy
  	INV-ONC-392 (ONC-392-001/Pro00033015/Chang) 6 mg/kg in dextrose 5% 500 mL	Dose: 6 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose			Offset: 30 Minutes	Instructions:	Administer intravenously using 0.2 micron inline filter over 90 minutes for initial infusion, then over 60 minutes for subsequent infusions. After the infusion, flush by adding 25mL of 0.9% NaCl to the IV bag to ensure all drug is infused. Prepared bag/syringe is stable for 4 hours at room temperature. 
Final concentration can be between 0.5mg/mL to 3mg/mL. 
HAZARDOUS - Handle with care
Caution: New Drug-Limited by Federal (USA) Law to Investigational use.

	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ONC-392 30 MG/ML INTRAVENOUS SOLN (ONC-392-001/PRO00033015/CHANG)	Medications	6 mg/kg	Main Ingredient	Yes	DEXTROSE 5 % IN WATER (D5W) INTRAVENOUS SOLUTION	QS Base	500 mL	Yes	Yes				Post-Hydration
  	sodium chloride 0.9 % infusion	Dose: --	Route: intravenous	continuous	Start: S					Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Post-infusion observation time is minimum 30 minutes (±10 minutes)
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
6. Notify the treating physician.
7. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
8. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain) 
1. Stop the infusion. 
2. Notify the CERT team and treating physician immediately. 
3. Place the patient on continuous monitoring. 
4. Obtain vital signs. 
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%. 
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing. 
7. Administer diphenhydramine 50 mg intravenous once and acetaminophen 650 mg once. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg  orally and Famotidine 20 mg intravenous once. 
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe). 
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician. 
10. If the infusion is interrupted, then restart the infusion at 50% of the original infusion rate when symptoms resolve.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 - SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise - cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg,  confusion, collapse, loss of consciousness, or incontinence) 
1. Stop the infusion. 
2. Notify the CERT team and treating physician immediately. 
3. Place the patient on continuous monitoring. 
4. Obtain vital signs. 
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position. 
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%. 
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing. 
8. Administer diphenhydramine 50 mg intravenous once and methylprednisolone 100 mg. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg  orally and Famotidine 20 mg intravenous once. 
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous. 
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 8	Interval: --	Occurrences: --	Comments:	Grade 4 Infusion Reaction: life-threatening; pressor or ventilator support indicated. See Emergency Medications. 
		  	ONC NURSING COMMUNICATION 9	Interval: --	Occurrences: --	Comments:	Treatment and safety management decisions all to be based upon local laboratory data.  Protocol does not provide reference ranges.
		  	sodium chloride 0.9 % infusion	Dose: 50-100 mL/hr	Route: intravenous	PRN	Start: S				  	sodium chloride 0.9 % infusion	Dose: 1,000 mL	Route: intravenous	PRN	Start: S				  	acetaminophen (TYLENOL) tablet 650 mg	Dose: 650 mg	Route: oral	PRN	Start: S				  	diphenhydrAMINE (BENADRYL) injection 50 mg	Dose: 50 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	methylPREDNISolone sodium succinate (Solu-MEDROL) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN	Start: S				  	epINEPHrine (ADRENALIN) injection 1 mg/mL 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 6	Repeat 1 time	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	ONC INFUSION APPOINTMENT REQUEST 5	Interval: --	Occurrences: --			Line Flush
  	sodium chloride 0.9% flush 25 mL	Dose: 25 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Please refer to Protocol Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: see 1.10.3 Study Schedule in Part C: Table 4: Study Schedule for Expansion Cohorts Part C Arm B. see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
		  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	Please refer to Section 7.9 Immune-mediated Adverse Reaction (IMAR) Management Plan and Table 12: Dose Modifications for IMARS: see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
		  	ONC NURSING COMMUNICATION 6	Interval: --	Occurrences: --	Comments:	Please refer to Protocol Section 7.10 Prophylactic and Acute Management of Infusion Reactions: Prophylaxis Pre-Medications, Post-Infusion Management, and Treatment Recommendations for Grade 1, 2, 3, 4 Symptoms  see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Taken within 20 minutes pre-infusion and 30 (±10) minutes of infusion completion
		  	MEASURE WEIGHT	Interval: --	Occurrences: --		  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	Physical Exam + ECOG
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	ABSOLUTE NEUTROPHIL COUNT	Interval: --	Occurrences: --		  	ABSOLUTE LYMPHOCYTE COUNT	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --			Labs
  	BILIRUBIN DIRECT	Interval: --	Occurrences: --			Labs
  	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --			Labs
  	CANCER ANTIGEN 125	Interval: --	Occurrences: --		  	CANCER ANTIGEN 15-3	Interval: --	Occurrences: --		  	MISCELLANEOUS REFERRAL TEST	Interval: --	Occurrences: --	Comments:	Cancer antigen 27-29 (CA-BR)
		  	CARCINOEMBRYONIC ANTIGEN (CEA)	Interval: --	Occurrences: --			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Nursing Orders
  	TREATMENT CONDITIONS 13	Interval: --	Occurrences: --	Comments:	HOLD and notify provider if 
o ANC LESS than 1000; 
o Platelets LESS than 100,000; 
o AST or ALT GREATER than 3 times ULN or total bilirubin GREATER than 1.5 times ULN; 
o Serum creatinine GREATER than 1.5x ULN or 1.5x ABOVE baseline.
			Provider Communication
  	ONC PROVIDER COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Dose adjustment allowed: 
Level 1: 6 mg/kg; 
Level 2: 3 mg/kg; 
Adjustment from 10 to 3 mg/kg is allowed. 
			Chemotherapy
  	INV-ONC-392 (ONC-392-001/Pro00033015/Chang) 6 mg/kg in dextrose 5% 500 mL	Dose: 6 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose			Offset: 30 Minutes	Instructions:	Administer intravenously using 0.2 micron inline filter over 90 minutes for initial infusion, then over 60 minutes for subsequent infusions. After the infusion, flush by adding 25mL of 0.9% NaCl to the IV bag to ensure all drug is infused. Prepared bag/syringe is stable for 4 hours at room temperature. 
Final concentration can be between 0.5mg/mL to 3mg/mL. 
HAZARDOUS - Handle with care
Caution: New Drug-Limited by Federal (USA) Law to Investigational use.

	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ONC-392 30 MG/ML INTRAVENOUS SOLN (ONC-392-001/PRO00033015/CHANG)	Medications	6 mg/kg	Main Ingredient	Yes	DEXTROSE 5 % IN WATER (D5W) INTRAVENOUS SOLUTION	QS Base	500 mL	Yes	Yes				Post-Hydration
  	sodium chloride 0.9 % infusion	Dose: --	Route: intravenous	continuous	Start: S					Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Post-infusion observation time is minimum 30 minutes (±10 minutes)
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
6. Notify the treating physician.
7. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
8. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain) 
1. Stop the infusion. 
2. Notify the CERT team and treating physician immediately. 
3. Place the patient on continuous monitoring. 
4. Obtain vital signs. 
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%. 
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing. 
7. Administer diphenhydramine 50 mg intravenous once and acetaminophen 650 mg once. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg  orally and Famotidine 20 mg intravenous once. 
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe). 
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician. 
10. If the infusion is interrupted, then restart the infusion at 50% of the original infusion rate when symptoms resolve.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 - SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise - cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg,  confusion, collapse, loss of consciousness, or incontinence) 
1. Stop the infusion. 
2. Notify the CERT team and treating physician immediately. 
3. Place the patient on continuous monitoring. 
4. Obtain vital signs. 
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position. 
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%. 
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing. 
8. Administer diphenhydramine 50 mg intravenous once and methylprednisolone 100 mg. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg  orally and Famotidine 20 mg intravenous once. 
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous. 
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 8	Interval: --	Occurrences: --	Comments:	Grade 4 Infusion Reaction: life-threatening; pressor or ventilator support indicated. See Emergency Medications. 
		  	ONC NURSING COMMUNICATION 9	Interval: --	Occurrences: --	Comments:	Treatment and safety management decisions all to be based upon local laboratory data.  Protocol does not provide reference ranges.
		  	sodium chloride 0.9 % infusion	Dose: 50-100 mL/hr	Route: intravenous	PRN	Start: S				  	sodium chloride 0.9 % infusion	Dose: 1,000 mL	Route: intravenous	PRN	Start: S				  	acetaminophen (TYLENOL) tablet 650 mg	Dose: 650 mg	Route: oral	PRN	Start: S				  	diphenhydrAMINE (BENADRYL) injection 50 mg	Dose: 50 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	methylPREDNISolone sodium succinate (Solu-MEDROL) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN	Start: S				  	epINEPHrine (ADRENALIN) injection 1 mg/mL 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled				Day 8	Perform every 1 day x1		Imaging
  	CT CHEST W CONTRAST ABDOMEN W CONTRAST PELVIS W CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI with preference for CT. If MRI is needed, please order as appropriate.
					
Cycle 7	Repeat 1 time	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	ONC INFUSION APPOINTMENT REQUEST 5	Interval: --	Occurrences: --			Line Flush
  	sodium chloride 0.9% flush 25 mL	Dose: 25 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Please refer to Protocol Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: see 1.10.3 Study Schedule in Part C: Table 4: Study Schedule for Expansion Cohorts Part C Arm B. see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
		  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	Please refer to Section 7.9 Immune-mediated Adverse Reaction (IMAR) Management Plan and Table 12: Dose Modifications for IMARS: see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
		  	ONC NURSING COMMUNICATION 6	Interval: --	Occurrences: --	Comments:	Please refer to Protocol Section 7.10 Prophylactic and Acute Management of Infusion Reactions: Prophylaxis Pre-Medications, Post-Infusion Management, and Treatment Recommendations for Grade 1, 2, 3, 4 Symptoms  see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Taken within 20 minutes pre-infusion and 30 (±10) minutes of infusion completion
		  	MEASURE WEIGHT	Interval: --	Occurrences: --		  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	Physical Exam + ECOG
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	ABSOLUTE NEUTROPHIL COUNT	Interval: --	Occurrences: --		  	ABSOLUTE LYMPHOCYTE COUNT	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --			Labs
  	BILIRUBIN DIRECT	Interval: --	Occurrences: --			Labs
  	LDH	Interval: --	Occurrences: --			Labs
  	THYROID STIMULATING HORMONE	Interval: --	Occurrences: --		  	T3	Interval: --	Occurrences: --		  	T4, FREE	Interval: --	Occurrences: --			Labs
  	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --			Labs
  	CANCER ANTIGEN 125	Interval: --	Occurrences: --		  	CANCER ANTIGEN 15-3	Interval: --	Occurrences: --		  	MISCELLANEOUS REFERRAL TEST	Interval: --	Occurrences: --	Comments:	Cancer antigen 27-29 (CA-BR)
		  	CARCINOEMBRYONIC ANTIGEN (CEA)	Interval: --	Occurrences: --			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Nursing Orders
  	TREATMENT CONDITIONS 13	Interval: --	Occurrences: --	Comments:	HOLD and notify provider if 
o ANC LESS than 1000; 
o Platelets LESS than 100,000; 
o AST or ALT GREATER than 3 times ULN or total bilirubin GREATER than 1.5 times ULN; 
o Serum creatinine GREATER than 1.5x ULN or 1.5x ABOVE baseline.
			Provider Communication
  	ONC PROVIDER COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Dose adjustment allowed: 
Level 1: 6 mg/kg; 
Level 2: 3 mg/kg; 
Adjustment from 10 to 3 mg/kg is allowed. 
			Chemotherapy
  	INV-ONC-392 (ONC-392-001/Pro00033015/Chang) 6 mg/kg in dextrose 5% 500 mL	Dose: 6 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose			Offset: 30 Minutes	Instructions:	Administer intravenously using 0.2 micron inline filter over 90 minutes for initial infusion, then over 60 minutes for subsequent infusions. After the infusion, flush by adding 25mL of 0.9% NaCl to the IV bag to ensure all drug is infused. Prepared bag/syringe is stable for 4 hours at room temperature. 
Final concentration can be between 0.5mg/mL to 3mg/mL. 
HAZARDOUS - Handle with care
Caution: New Drug-Limited by Federal (USA) Law to Investigational use.

	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ONC-392 30 MG/ML INTRAVENOUS SOLN (ONC-392-001/PRO00033015/CHANG)	Medications	6 mg/kg	Main Ingredient	Yes	DEXTROSE 5 % IN WATER (D5W) INTRAVENOUS SOLUTION	QS Base	500 mL	Yes	Yes				Post-Hydration
  	sodium chloride 0.9 % infusion	Dose: --	Route: intravenous	continuous	Start: S					Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Post-infusion observation time is minimum 30 minutes (±10 minutes)
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
6. Notify the treating physician.
7. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
8. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain) 
1. Stop the infusion. 
2. Notify the CERT team and treating physician immediately. 
3. Place the patient on continuous monitoring. 
4. Obtain vital signs. 
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%. 
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing. 
7. Administer diphenhydramine 50 mg intravenous once and acetaminophen 650 mg once. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg  orally and Famotidine 20 mg intravenous once. 
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe). 
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician. 
10. If the infusion is interrupted, then restart the infusion at 50% of the original infusion rate when symptoms resolve.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 - SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise - cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg,  confusion, collapse, loss of consciousness, or incontinence) 
1. Stop the infusion. 
2. Notify the CERT team and treating physician immediately. 
3. Place the patient on continuous monitoring. 
4. Obtain vital signs. 
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position. 
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%. 
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing. 
8. Administer diphenhydramine 50 mg intravenous once and methylprednisolone 100 mg. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg  orally and Famotidine 20 mg intravenous once. 
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous. 
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 8	Interval: --	Occurrences: --	Comments:	Grade 4 Infusion Reaction: life-threatening; pressor or ventilator support indicated. See Emergency Medications. 
		  	ONC NURSING COMMUNICATION 9	Interval: --	Occurrences: --	Comments:	Treatment and safety management decisions all to be based upon local laboratory data.  Protocol does not provide reference ranges.
		  	sodium chloride 0.9 % infusion	Dose: 50-100 mL/hr	Route: intravenous	PRN	Start: S				  	sodium chloride 0.9 % infusion	Dose: 1,000 mL	Route: intravenous	PRN	Start: S				  	acetaminophen (TYLENOL) tablet 650 mg	Dose: 650 mg	Route: oral	PRN	Start: S				  	diphenhydrAMINE (BENADRYL) injection 50 mg	Dose: 50 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	methylPREDNISolone sodium succinate (Solu-MEDROL) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN	Start: S				  	epINEPHrine (ADRENALIN) injection 1 mg/mL 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 8	Repeat 1 time	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	ONC INFUSION APPOINTMENT REQUEST 5	Interval: --	Occurrences: --			Line Flush
  	sodium chloride 0.9% flush 25 mL	Dose: 25 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Please refer to Protocol Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: see 1.10.3 Study Schedule in Part C: Table 4: Study Schedule for Expansion Cohorts Part C Arm B. see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
		  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	Please refer to Section 7.9 Immune-mediated Adverse Reaction (IMAR) Management Plan and Table 12: Dose Modifications for IMARS: see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
		  	ONC NURSING COMMUNICATION 6	Interval: --	Occurrences: --	Comments:	Please refer to Protocol Section 7.10 Prophylactic and Acute Management of Infusion Reactions: Prophylaxis Pre-Medications, Post-Infusion Management, and Treatment Recommendations for Grade 1, 2, 3, 4 Symptoms  see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Taken within 20 minutes pre-infusion and 30 (±10) minutes of infusion completion
		  	MEASURE WEIGHT	Interval: --	Occurrences: --		  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	Physical Exam + ECOG
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	ABSOLUTE NEUTROPHIL COUNT	Interval: --	Occurrences: --		  	ABSOLUTE LYMPHOCYTE COUNT	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --			Labs
  	BILIRUBIN DIRECT	Interval: --	Occurrences: --			Labs
  	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --			Labs
  	CANCER ANTIGEN 125	Interval: --	Occurrences: --		  	CANCER ANTIGEN 15-3	Interval: --	Occurrences: --		  	MISCELLANEOUS REFERRAL TEST	Interval: --	Occurrences: --	Comments:	Cancer antigen 27-29 (CA-BR)
		  	CARCINOEMBRYONIC ANTIGEN (CEA)	Interval: --	Occurrences: --			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Nursing Orders
  	TREATMENT CONDITIONS 13	Interval: --	Occurrences: --	Comments:	HOLD and notify provider if 
o ANC LESS than 1000; 
o Platelets LESS than 100,000; 
o AST or ALT GREATER than 3 times ULN or total bilirubin GREATER than 1.5 times ULN; 
o Serum creatinine GREATER than 1.5x ULN or 1.5x ABOVE baseline.
			Provider Communication
  	ONC PROVIDER COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Dose adjustment allowed: 
Level 1: 6 mg/kg; 
Level 2: 3 mg/kg; 
Adjustment from 10 to 3 mg/kg is allowed. 
			Chemotherapy
  	INV-ONC-392 (ONC-392-001/Pro00033015/Chang) 6 mg/kg in dextrose 5% 500 mL	Dose: 6 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose			Offset: 30 Minutes	Instructions:	Administer intravenously using 0.2 micron inline filter over 90 minutes for initial infusion, then over 60 minutes for subsequent infusions. After the infusion, flush by adding 25mL of 0.9% NaCl to the IV bag to ensure all drug is infused. Prepared bag/syringe is stable for 4 hours at room temperature. 
Final concentration can be between 0.5mg/mL to 3mg/mL. 
HAZARDOUS - Handle with care
Caution: New Drug-Limited by Federal (USA) Law to Investigational use.

	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ONC-392 30 MG/ML INTRAVENOUS SOLN (ONC-392-001/PRO00033015/CHANG)	Medications	6 mg/kg	Main Ingredient	Yes	DEXTROSE 5 % IN WATER (D5W) INTRAVENOUS SOLUTION	QS Base	500 mL	Yes	Yes				Post-Hydration
  	sodium chloride 0.9 % infusion	Dose: --	Route: intravenous	continuous	Start: S					Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Post-infusion observation time is minimum 30 minutes (±10 minutes)
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
6. Notify the treating physician.
7. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
8. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain) 
1. Stop the infusion. 
2. Notify the CERT team and treating physician immediately. 
3. Place the patient on continuous monitoring. 
4. Obtain vital signs. 
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%. 
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing. 
7. Administer diphenhydramine 50 mg intravenous once and acetaminophen 650 mg once. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg  orally and Famotidine 20 mg intravenous once. 
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe). 
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician. 
10. If the infusion is interrupted, then restart the infusion at 50% of the original infusion rate when symptoms resolve.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 - SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise - cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg,  confusion, collapse, loss of consciousness, or incontinence) 
1. Stop the infusion. 
2. Notify the CERT team and treating physician immediately. 
3. Place the patient on continuous monitoring. 
4. Obtain vital signs. 
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position. 
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%. 
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing. 
8. Administer diphenhydramine 50 mg intravenous once and methylprednisolone 100 mg. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg  orally and Famotidine 20 mg intravenous once. 
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous. 
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 8	Interval: --	Occurrences: --	Comments:	Grade 4 Infusion Reaction: life-threatening; pressor or ventilator support indicated. See Emergency Medications. 
		  	ONC NURSING COMMUNICATION 9	Interval: --	Occurrences: --	Comments:	Treatment and safety management decisions all to be based upon local laboratory data.  Protocol does not provide reference ranges.
		  	sodium chloride 0.9 % infusion	Dose: 50-100 mL/hr	Route: intravenous	PRN	Start: S				  	sodium chloride 0.9 % infusion	Dose: 1,000 mL	Route: intravenous	PRN	Start: S				  	acetaminophen (TYLENOL) tablet 650 mg	Dose: 650 mg	Route: oral	PRN	Start: S				  	diphenhydrAMINE (BENADRYL) injection 50 mg	Dose: 50 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	methylPREDNISolone sodium succinate (Solu-MEDROL) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN	Start: S				  	epINEPHrine (ADRENALIN) injection 1 mg/mL 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 9	Repeat 1 time	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	ONC INFUSION APPOINTMENT REQUEST 5	Interval: --	Occurrences: --			Line Flush
  	sodium chloride 0.9% flush 25 mL	Dose: 25 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Please refer to Protocol Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: see 1.10.3 Study Schedule in Part C: Table 4: Study Schedule for Expansion Cohorts Part C Arm B. see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
		  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	Please refer to Section 7.9 Immune-mediated Adverse Reaction (IMAR) Management Plan and Table 12: Dose Modifications for IMARS: see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
		  	ONC NURSING COMMUNICATION 6	Interval: --	Occurrences: --	Comments:	Please refer to Protocol Section 7.10 Prophylactic and Acute Management of Infusion Reactions: Prophylaxis Pre-Medications, Post-Infusion Management, and Treatment Recommendations for Grade 1, 2, 3, 4 Symptoms  see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Taken within 20 minutes pre-infusion and 30 (±10) minutes of infusion completion
		  	MEASURE WEIGHT	Interval: --	Occurrences: --		  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	Physical Exam + ECOG
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	ABSOLUTE NEUTROPHIL COUNT	Interval: --	Occurrences: --		  	ABSOLUTE LYMPHOCYTE COUNT	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --			Labs
  	BILIRUBIN DIRECT	Interval: --	Occurrences: --			Labs
  	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --			Labs
  	CANCER ANTIGEN 125	Interval: --	Occurrences: --		  	CANCER ANTIGEN 15-3	Interval: --	Occurrences: --		  	MISCELLANEOUS REFERRAL TEST	Interval: --	Occurrences: --	Comments:	Cancer antigen 27-29 (CA-BR)
		  	CARCINOEMBRYONIC ANTIGEN (CEA)	Interval: --	Occurrences: --			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Nursing Orders
  	TREATMENT CONDITIONS 13	Interval: --	Occurrences: --	Comments:	HOLD and notify provider if 
o ANC LESS than 1000; 
o Platelets LESS than 100,000; 
o AST or ALT GREATER than 3 times ULN or total bilirubin GREATER than 1.5 times ULN; 
o Serum creatinine GREATER than 1.5x ULN or 1.5x ABOVE baseline.
			Provider Communication
  	ONC PROVIDER COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Dose adjustment allowed: 
Level 1: 6 mg/kg; 
Level 2: 3 mg/kg; 
Adjustment from 10 to 3 mg/kg is allowed. 
			Chemotherapy
  	INV-ONC-392 (ONC-392-001/Pro00033015/Chang) 6 mg/kg in dextrose 5% 500 mL	Dose: 6 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose			Offset: 30 Minutes	Instructions:	Administer intravenously using 0.2 micron inline filter over 90 minutes for initial infusion, then over 60 minutes for subsequent infusions. After the infusion, flush by adding 25mL of 0.9% NaCl to the IV bag to ensure all drug is infused. Prepared bag/syringe is stable for 4 hours at room temperature. 
Final concentration can be between 0.5mg/mL to 3mg/mL. 
HAZARDOUS - Handle with care
Caution: New Drug-Limited by Federal (USA) Law to Investigational use.

	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ONC-392 30 MG/ML INTRAVENOUS SOLN (ONC-392-001/PRO00033015/CHANG)	Medications	6 mg/kg	Main Ingredient	Yes	DEXTROSE 5 % IN WATER (D5W) INTRAVENOUS SOLUTION	QS Base	500 mL	Yes	Yes				Post-Hydration
  	sodium chloride 0.9 % infusion	Dose: --	Route: intravenous	continuous	Start: S					Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Post-infusion observation time is minimum 30 minutes (±10 minutes)
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
6. Notify the treating physician.
7. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
8. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain) 
1. Stop the infusion. 
2. Notify the CERT team and treating physician immediately. 
3. Place the patient on continuous monitoring. 
4. Obtain vital signs. 
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%. 
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing. 
7. Administer diphenhydramine 50 mg intravenous once and acetaminophen 650 mg once. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg  orally and Famotidine 20 mg intravenous once. 
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe). 
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician. 
10. If the infusion is interrupted, then restart the infusion at 50% of the original infusion rate when symptoms resolve.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 - SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise - cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg,  confusion, collapse, loss of consciousness, or incontinence) 
1. Stop the infusion. 
2. Notify the CERT team and treating physician immediately. 
3. Place the patient on continuous monitoring. 
4. Obtain vital signs. 
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position. 
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%. 
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing. 
8. Administer diphenhydramine 50 mg intravenous once and methylprednisolone 100 mg. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg  orally and Famotidine 20 mg intravenous once. 
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous. 
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 8	Interval: --	Occurrences: --	Comments:	Grade 4 Infusion Reaction: life-threatening; pressor or ventilator support indicated. See Emergency Medications. 
		  	ONC NURSING COMMUNICATION 9	Interval: --	Occurrences: --	Comments:	Treatment and safety management decisions all to be based upon local laboratory data.  Protocol does not provide reference ranges.
		  	sodium chloride 0.9 % infusion	Dose: 50-100 mL/hr	Route: intravenous	PRN	Start: S				  	sodium chloride 0.9 % infusion	Dose: 1,000 mL	Route: intravenous	PRN	Start: S				  	acetaminophen (TYLENOL) tablet 650 mg	Dose: 650 mg	Route: oral	PRN	Start: S				  	diphenhydrAMINE (BENADRYL) injection 50 mg	Dose: 50 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	methylPREDNISolone sodium succinate (Solu-MEDROL) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN	Start: S				  	epINEPHrine (ADRENALIN) injection 1 mg/mL 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled				Day 8	Perform every 1 day x1		Imaging
  	CT CHEST W CONTRAST ABDOMEN W CONTRAST PELVIS W CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI with preference for CT. If MRI is needed, please order as appropriate.
					
Cycle 10	Repeat 1 time	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	ONC INFUSION APPOINTMENT REQUEST 5	Interval: --	Occurrences: --			Line Flush
  	sodium chloride 0.9% flush 25 mL	Dose: 25 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Please refer to Protocol Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: see 1.10.3 Study Schedule in Part C: Table 4: Study Schedule for Expansion Cohorts Part C Arm B. see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
		  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	Please refer to Section 7.9 Immune-mediated Adverse Reaction (IMAR) Management Plan and Table 12: Dose Modifications for IMARS: see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
		  	ONC NURSING COMMUNICATION 6	Interval: --	Occurrences: --	Comments:	Please refer to Protocol Section 7.10 Prophylactic and Acute Management of Infusion Reactions: Prophylaxis Pre-Medications, Post-Infusion Management, and Treatment Recommendations for Grade 1, 2, 3, 4 Symptoms  see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Taken within 20 minutes pre-infusion and 30 (±10) minutes of infusion completion
		  	MEASURE WEIGHT	Interval: --	Occurrences: --		  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	Physical Exam + ECOG
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	ABSOLUTE NEUTROPHIL COUNT	Interval: --	Occurrences: --		  	ABSOLUTE LYMPHOCYTE COUNT	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --			Labs
  	BILIRUBIN DIRECT	Interval: --	Occurrences: --			Labs
  	LDH	Interval: --	Occurrences: --			Labs
  	THYROID STIMULATING HORMONE	Interval: --	Occurrences: --		  	T3	Interval: --	Occurrences: --		  	T4, FREE	Interval: --	Occurrences: --			Labs
  	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --			Labs
  	CANCER ANTIGEN 125	Interval: --	Occurrences: --		  	CANCER ANTIGEN 15-3	Interval: --	Occurrences: --		  	MISCELLANEOUS REFERRAL TEST	Interval: --	Occurrences: --	Comments:	Cancer antigen 27-29 (CA-BR)
		  	CARCINOEMBRYONIC ANTIGEN (CEA)	Interval: --	Occurrences: --			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Nursing Orders
  	TREATMENT CONDITIONS 13	Interval: --	Occurrences: --	Comments:	HOLD and notify provider if 
o ANC LESS than 1000; 
o Platelets LESS than 100,000; 
o AST or ALT GREATER than 3 times ULN or total bilirubin GREATER than 1.5 times ULN; 
o Serum creatinine GREATER than 1.5x ULN or 1.5x ABOVE baseline.
			Provider Communication
  	ONC PROVIDER COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Dose adjustment allowed: 
Level 1: 6 mg/kg; 
Level 2: 3 mg/kg; 
Adjustment from 10 to 3 mg/kg is allowed. 
			Chemotherapy
  	INV-ONC-392 (ONC-392-001/Pro00033015/Chang) 6 mg/kg in dextrose 5% 500 mL	Dose: 6 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose			Offset: 30 Minutes	Instructions:	Administer intravenously using 0.2 micron inline filter over 90 minutes for initial infusion, then over 60 minutes for subsequent infusions. After the infusion, flush by adding 25mL of 0.9% NaCl to the IV bag to ensure all drug is infused. Prepared bag/syringe is stable for 4 hours at room temperature. 
Final concentration can be between 0.5mg/mL to 3mg/mL. 
HAZARDOUS - Handle with care
Caution: New Drug-Limited by Federal (USA) Law to Investigational use.

	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ONC-392 30 MG/ML INTRAVENOUS SOLN (ONC-392-001/PRO00033015/CHANG)	Medications	6 mg/kg	Main Ingredient	Yes	DEXTROSE 5 % IN WATER (D5W) INTRAVENOUS SOLUTION	QS Base	500 mL	Yes	Yes				Post-Hydration
  	sodium chloride 0.9 % infusion	Dose: --	Route: intravenous	continuous	Start: S					Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Post-infusion observation time is minimum 30 minutes (±10 minutes)
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
6. Notify the treating physician.
7. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
8. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain) 
1. Stop the infusion. 
2. Notify the CERT team and treating physician immediately. 
3. Place the patient on continuous monitoring. 
4. Obtain vital signs. 
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%. 
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing. 
7. Administer diphenhydramine 50 mg intravenous once and acetaminophen 650 mg once. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg  orally and Famotidine 20 mg intravenous once. 
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe). 
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician. 
10. If the infusion is interrupted, then restart the infusion at 50% of the original infusion rate when symptoms resolve.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 - SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise - cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg,  confusion, collapse, loss of consciousness, or incontinence) 
1. Stop the infusion. 
2. Notify the CERT team and treating physician immediately. 
3. Place the patient on continuous monitoring. 
4. Obtain vital signs. 
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position. 
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%. 
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing. 
8. Administer diphenhydramine 50 mg intravenous once and methylprednisolone 100 mg. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg  orally and Famotidine 20 mg intravenous once. 
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous. 
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 8	Interval: --	Occurrences: --	Comments:	Grade 4 Infusion Reaction: life-threatening; pressor or ventilator support indicated. See Emergency Medications. 
		  	ONC NURSING COMMUNICATION 9	Interval: --	Occurrences: --	Comments:	Treatment and safety management decisions all to be based upon local laboratory data.  Protocol does not provide reference ranges.
		  	sodium chloride 0.9 % infusion	Dose: 50-100 mL/hr	Route: intravenous	PRN	Start: S				  	sodium chloride 0.9 % infusion	Dose: 1,000 mL	Route: intravenous	PRN	Start: S				  	acetaminophen (TYLENOL) tablet 650 mg	Dose: 650 mg	Route: oral	PRN	Start: S				  	diphenhydrAMINE (BENADRYL) injection 50 mg	Dose: 50 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	methylPREDNISolone sodium succinate (Solu-MEDROL) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN	Start: S				  	epINEPHrine (ADRENALIN) injection 1 mg/mL 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 11	Repeat 1 time	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	ONC INFUSION APPOINTMENT REQUEST 5	Interval: --	Occurrences: --			Line Flush
  	sodium chloride 0.9% flush 25 mL	Dose: 25 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Please refer to Protocol Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: see 1.10.3 Study Schedule in Part C: Table 4: Study Schedule for Expansion Cohorts Part C Arm B. see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
		  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	Please refer to Section 7.9 Immune-mediated Adverse Reaction (IMAR) Management Plan and Table 12: Dose Modifications for IMARS: see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
		  	ONC NURSING COMMUNICATION 6	Interval: --	Occurrences: --	Comments:	Please refer to Protocol Section 7.10 Prophylactic and Acute Management of Infusion Reactions: Prophylaxis Pre-Medications, Post-Infusion Management, and Treatment Recommendations for Grade 1, 2, 3, 4 Symptoms  see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Taken within 20 minutes pre-infusion and 30 (±10) minutes of infusion completion
		  	MEASURE WEIGHT	Interval: --	Occurrences: --		  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	Physical Exam + ECOG
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	ABSOLUTE NEUTROPHIL COUNT	Interval: --	Occurrences: --		  	ABSOLUTE LYMPHOCYTE COUNT	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --			Labs
  	BILIRUBIN DIRECT	Interval: --	Occurrences: --			Labs
  	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --			Labs
  	CANCER ANTIGEN 125	Interval: --	Occurrences: --		  	CANCER ANTIGEN 15-3	Interval: --	Occurrences: --		  	MISCELLANEOUS REFERRAL TEST	Interval: --	Occurrences: --	Comments:	Cancer antigen 27-29 (CA-BR)
		  	CARCINOEMBRYONIC ANTIGEN (CEA)	Interval: --	Occurrences: --			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Nursing Orders
  	TREATMENT CONDITIONS 13	Interval: --	Occurrences: --	Comments:	HOLD and notify provider if 
o ANC LESS than 1000; 
o Platelets LESS than 100,000; 
o AST or ALT GREATER than 3 times ULN or total bilirubin GREATER than 1.5 times ULN; 
o Serum creatinine GREATER than 1.5x ULN or 1.5x ABOVE baseline.
			Provider Communication
  	ONC PROVIDER COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Dose adjustment allowed: 
Level 1: 6 mg/kg; 
Level 2: 3 mg/kg; 
Adjustment from 10 to 3 mg/kg is allowed. 
			Chemotherapy
  	INV-ONC-392 (ONC-392-001/Pro00033015/Chang) 6 mg/kg in dextrose 5% 500 mL	Dose: 6 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose			Offset: 30 Minutes	Instructions:	Administer intravenously using 0.2 micron inline filter over 90 minutes for initial infusion, then over 60 minutes for subsequent infusions. After the infusion, flush by adding 25mL of 0.9% NaCl to the IV bag to ensure all drug is infused. Prepared bag/syringe is stable for 4 hours at room temperature. 
Final concentration can be between 0.5mg/mL to 3mg/mL. 
HAZARDOUS - Handle with care
Caution: New Drug-Limited by Federal (USA) Law to Investigational use.

	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ONC-392 30 MG/ML INTRAVENOUS SOLN (ONC-392-001/PRO00033015/CHANG)	Medications	6 mg/kg	Main Ingredient	Yes	DEXTROSE 5 % IN WATER (D5W) INTRAVENOUS SOLUTION	QS Base	500 mL	Yes	Yes				Post-Hydration
  	sodium chloride 0.9 % infusion	Dose: --	Route: intravenous	continuous	Start: S					Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Post-infusion observation time is minimum 30 minutes (±10 minutes)
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
6. Notify the treating physician.
7. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
8. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain) 
1. Stop the infusion. 
2. Notify the CERT team and treating physician immediately. 
3. Place the patient on continuous monitoring. 
4. Obtain vital signs. 
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%. 
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing. 
7. Administer diphenhydramine 50 mg intravenous once and acetaminophen 650 mg once. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg  orally and Famotidine 20 mg intravenous once. 
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe). 
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician. 
10. If the infusion is interrupted, then restart the infusion at 50% of the original infusion rate when symptoms resolve.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 - SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise - cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg,  confusion, collapse, loss of consciousness, or incontinence) 
1. Stop the infusion. 
2. Notify the CERT team and treating physician immediately. 
3. Place the patient on continuous monitoring. 
4. Obtain vital signs. 
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position. 
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%. 
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing. 
8. Administer diphenhydramine 50 mg intravenous once and methylprednisolone 100 mg. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg  orally and Famotidine 20 mg intravenous once. 
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous. 
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 8	Interval: --	Occurrences: --	Comments:	Grade 4 Infusion Reaction: life-threatening; pressor or ventilator support indicated. See Emergency Medications. 
		  	ONC NURSING COMMUNICATION 9	Interval: --	Occurrences: --	Comments:	Treatment and safety management decisions all to be based upon local laboratory data.  Protocol does not provide reference ranges.
		  	sodium chloride 0.9 % infusion	Dose: 50-100 mL/hr	Route: intravenous	PRN	Start: S				  	sodium chloride 0.9 % infusion	Dose: 1,000 mL	Route: intravenous	PRN	Start: S				  	acetaminophen (TYLENOL) tablet 650 mg	Dose: 650 mg	Route: oral	PRN	Start: S				  	diphenhydrAMINE (BENADRYL) injection 50 mg	Dose: 50 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	methylPREDNISolone sodium succinate (Solu-MEDROL) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN	Start: S				  	epINEPHrine (ADRENALIN) injection 1 mg/mL 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 12	Repeat 1 time	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	ONC INFUSION APPOINTMENT REQUEST 5	Interval: --	Occurrences: --			Line Flush
  	sodium chloride 0.9% flush 25 mL	Dose: 25 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Please refer to Protocol Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: see 1.10.3 Study Schedule in Part C: Table 4: Study Schedule for Expansion Cohorts Part C Arm B. see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
		  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	Please refer to Section 7.9 Immune-mediated Adverse Reaction (IMAR) Management Plan and Table 12: Dose Modifications for IMARS: see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
		  	ONC NURSING COMMUNICATION 6	Interval: --	Occurrences: --	Comments:	Please refer to Protocol Section 7.10 Prophylactic and Acute Management of Infusion Reactions: Prophylaxis Pre-Medications, Post-Infusion Management, and Treatment Recommendations for Grade 1, 2, 3, 4 Symptoms  see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Taken within 20 minutes pre-infusion and 30 (±10) minutes of infusion completion
		  	MEASURE WEIGHT	Interval: --	Occurrences: --		  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	Physical Exam + ECOG
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	ABSOLUTE NEUTROPHIL COUNT	Interval: --	Occurrences: --		  	ABSOLUTE LYMPHOCYTE COUNT	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --			Labs
  	BILIRUBIN DIRECT	Interval: --	Occurrences: --			Labs
  	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --			Labs
  	CANCER ANTIGEN 125	Interval: --	Occurrences: --		  	CANCER ANTIGEN 15-3	Interval: --	Occurrences: --		  	MISCELLANEOUS REFERRAL TEST	Interval: --	Occurrences: --	Comments:	Cancer antigen 27-29 (CA-BR)
		  	CARCINOEMBRYONIC ANTIGEN (CEA)	Interval: --	Occurrences: --			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Nursing Orders
  	TREATMENT CONDITIONS 13	Interval: --	Occurrences: --	Comments:	HOLD and notify provider if 
o ANC LESS than 1000; 
o Platelets LESS than 100,000; 
o AST or ALT GREATER than 3 times ULN or total bilirubin GREATER than 1.5 times ULN; 
o Serum creatinine GREATER than 1.5x ULN or 1.5x ABOVE baseline.
			Provider Communication
  	ONC PROVIDER COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Dose adjustment allowed: 
Level 1: 6 mg/kg; 
Level 2: 3 mg/kg; 
Adjustment from 10 to 3 mg/kg is allowed. 
			Chemotherapy
  	INV-ONC-392 (ONC-392-001/Pro00033015/Chang) 6 mg/kg in dextrose 5% 500 mL	Dose: 6 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose			Offset: 30 Minutes	Instructions:	Administer intravenously using 0.2 micron inline filter over 90 minutes for initial infusion, then over 60 minutes for subsequent infusions. After the infusion, flush by adding 25mL of 0.9% NaCl to the IV bag to ensure all drug is infused. Prepared bag/syringe is stable for 4 hours at room temperature. 
Final concentration can be between 0.5mg/mL to 3mg/mL. 
HAZARDOUS - Handle with care
Caution: New Drug-Limited by Federal (USA) Law to Investigational use.

	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ONC-392 30 MG/ML INTRAVENOUS SOLN (ONC-392-001/PRO00033015/CHANG)	Medications	6 mg/kg	Main Ingredient	Yes	DEXTROSE 5 % IN WATER (D5W) INTRAVENOUS SOLUTION	QS Base	500 mL	Yes	Yes				Post-Hydration
  	sodium chloride 0.9 % infusion	Dose: --	Route: intravenous	continuous	Start: S					Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Post-infusion observation time is minimum 30 minutes (±10 minutes)
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
6. Notify the treating physician.
7. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
8. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain) 
1. Stop the infusion. 
2. Notify the CERT team and treating physician immediately. 
3. Place the patient on continuous monitoring. 
4. Obtain vital signs. 
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%. 
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing. 
7. Administer diphenhydramine 50 mg intravenous once and acetaminophen 650 mg once. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg  orally and Famotidine 20 mg intravenous once. 
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe). 
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician. 
10. If the infusion is interrupted, then restart the infusion at 50% of the original infusion rate when symptoms resolve.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 - SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise - cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg,  confusion, collapse, loss of consciousness, or incontinence) 
1. Stop the infusion. 
2. Notify the CERT team and treating physician immediately. 
3. Place the patient on continuous monitoring. 
4. Obtain vital signs. 
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position. 
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%. 
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing. 
8. Administer diphenhydramine 50 mg intravenous once and methylprednisolone 100 mg. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg  orally and Famotidine 20 mg intravenous once. 
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous. 
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 8	Interval: --	Occurrences: --	Comments:	Grade 4 Infusion Reaction: life-threatening; pressor or ventilator support indicated. See Emergency Medications. 
		  	ONC NURSING COMMUNICATION 9	Interval: --	Occurrences: --	Comments:	Treatment and safety management decisions all to be based upon local laboratory data.  Protocol does not provide reference ranges.
		  	sodium chloride 0.9 % infusion	Dose: 50-100 mL/hr	Route: intravenous	PRN	Start: S				  	sodium chloride 0.9 % infusion	Dose: 1,000 mL	Route: intravenous	PRN	Start: S				  	acetaminophen (TYLENOL) tablet 650 mg	Dose: 650 mg	Route: oral	PRN	Start: S				  	diphenhydrAMINE (BENADRYL) injection 50 mg	Dose: 50 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	methylPREDNISolone sodium succinate (Solu-MEDROL) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN	Start: S				  	epINEPHrine (ADRENALIN) injection 1 mg/mL 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled				Day 8	Perform every 1 day x1		Imaging
  	CT CHEST W CONTRAST ABDOMEN W CONTRAST PELVIS W CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI with preference for CT. If MRI is needed, please order as appropriate.
					
Cycle 13	Repeat 1 time	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	ONC INFUSION APPOINTMENT REQUEST 5	Interval: --	Occurrences: --			Line Flush
  	sodium chloride 0.9% flush 25 mL	Dose: 25 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Please refer to Protocol Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: see 1.10.3 Study Schedule in Part C: Table 4: Study Schedule for Expansion Cohorts Part C Arm B. see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
		  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	Please refer to Section 7.9 Immune-mediated Adverse Reaction (IMAR) Management Plan and Table 12: Dose Modifications for IMARS: see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
		  	ONC NURSING COMMUNICATION 6	Interval: --	Occurrences: --	Comments:	Please refer to Protocol Section 7.10 Prophylactic and Acute Management of Infusion Reactions: Prophylaxis Pre-Medications, Post-Infusion Management, and Treatment Recommendations for Grade 1, 2, 3, 4 Symptoms  see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Taken within 20 minutes pre-infusion and 30 (±10) minutes of infusion completion
		  	MEASURE WEIGHT	Interval: --	Occurrences: --		  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	Physical Exam + ECOG
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	ABSOLUTE NEUTROPHIL COUNT	Interval: --	Occurrences: --		  	ABSOLUTE LYMPHOCYTE COUNT	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --			Labs
  	BILIRUBIN DIRECT	Interval: --	Occurrences: --			Labs
  	LDH	Interval: --	Occurrences: --			Labs
  	THYROID STIMULATING HORMONE	Interval: --	Occurrences: --		  	T3	Interval: --	Occurrences: --		  	T4, FREE	Interval: --	Occurrences: --			Labs
  	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --			Labs
  	CANCER ANTIGEN 125	Interval: --	Occurrences: --		  	CANCER ANTIGEN 15-3	Interval: --	Occurrences: --		  	MISCELLANEOUS REFERRAL TEST	Interval: --	Occurrences: --	Comments:	Cancer antigen 27-29 (CA-BR)
		  	CARCINOEMBRYONIC ANTIGEN (CEA)	Interval: --	Occurrences: --			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Nursing Orders
  	TREATMENT CONDITIONS 13	Interval: --	Occurrences: --	Comments:	HOLD and notify provider if 
o ANC LESS than 1000; 
o Platelets LESS than 100,000; 
o AST or ALT GREATER than 3 times ULN or total bilirubin GREATER than 1.5 times ULN; 
o Serum creatinine GREATER than 1.5x ULN or 1.5x ABOVE baseline.
			Provider Communication
  	ONC PROVIDER COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Dose adjustment allowed: 
Level 1: 6 mg/kg; 
Level 2: 3 mg/kg; 
Adjustment from 10 to 3 mg/kg is allowed. 
			Chemotherapy
  	INV-ONC-392 (ONC-392-001/Pro00033015/Chang) 6 mg/kg in dextrose 5% 500 mL	Dose: 6 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose			Offset: 30 Minutes	Instructions:	Administer intravenously using 0.2 micron inline filter over 90 minutes for initial infusion, then over 60 minutes for subsequent infusions. After the infusion, flush by adding 25mL of 0.9% NaCl to the IV bag to ensure all drug is infused. Prepared bag/syringe is stable for 4 hours at room temperature. 
Final concentration can be between 0.5mg/mL to 3mg/mL. 
HAZARDOUS - Handle with care
Caution: New Drug-Limited by Federal (USA) Law to Investigational use.

	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ONC-392 30 MG/ML INTRAVENOUS SOLN (ONC-392-001/PRO00033015/CHANG)	Medications	6 mg/kg	Main Ingredient	Yes	DEXTROSE 5 % IN WATER (D5W) INTRAVENOUS SOLUTION	QS Base	500 mL	Yes	Yes				Post-Hydration
  	sodium chloride 0.9 % infusion	Dose: --	Route: intravenous	continuous	Start: S					Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Post-infusion observation time is minimum 30 minutes (±10 minutes)
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
6. Notify the treating physician.
7. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
8. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain) 
1. Stop the infusion. 
2. Notify the CERT team and treating physician immediately. 
3. Place the patient on continuous monitoring. 
4. Obtain vital signs. 
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%. 
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing. 
7. Administer diphenhydramine 50 mg intravenous once and acetaminophen 650 mg once. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg  orally and Famotidine 20 mg intravenous once. 
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe). 
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician. 
10. If the infusion is interrupted, then restart the infusion at 50% of the original infusion rate when symptoms resolve.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 - SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise - cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg,  confusion, collapse, loss of consciousness, or incontinence) 
1. Stop the infusion. 
2. Notify the CERT team and treating physician immediately. 
3. Place the patient on continuous monitoring. 
4. Obtain vital signs. 
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position. 
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%. 
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing. 
8. Administer diphenhydramine 50 mg intravenous once and methylprednisolone 100 mg. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg  orally and Famotidine 20 mg intravenous once. 
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous. 
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 8	Interval: --	Occurrences: --	Comments:	Grade 4 Infusion Reaction: life-threatening; pressor or ventilator support indicated. See Emergency Medications. 
		  	ONC NURSING COMMUNICATION 9	Interval: --	Occurrences: --	Comments:	Treatment and safety management decisions all to be based upon local laboratory data.  Protocol does not provide reference ranges.
		  	sodium chloride 0.9 % infusion	Dose: 50-100 mL/hr	Route: intravenous	PRN	Start: S				  	sodium chloride 0.9 % infusion	Dose: 1,000 mL	Route: intravenous	PRN	Start: S				  	acetaminophen (TYLENOL) tablet 650 mg	Dose: 650 mg	Route: oral	PRN	Start: S				  	diphenhydrAMINE (BENADRYL) injection 50 mg	Dose: 50 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	methylPREDNISolone sodium succinate (Solu-MEDROL) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN	Start: S				  	epINEPHrine (ADRENALIN) injection 1 mg/mL 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 14	Repeat 1 time	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	ONC INFUSION APPOINTMENT REQUEST 5	Interval: --	Occurrences: --			Line Flush
  	sodium chloride 0.9% flush 25 mL	Dose: 25 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Please refer to Protocol Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: see 1.10.3 Study Schedule in Part C: Table 4: Study Schedule for Expansion Cohorts Part C Arm B. see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
		  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	Please refer to Section 7.9 Immune-mediated Adverse Reaction (IMAR) Management Plan and Table 12: Dose Modifications for IMARS: see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
		  	ONC NURSING COMMUNICATION 6	Interval: --	Occurrences: --	Comments:	Please refer to Protocol Section 7.10 Prophylactic and Acute Management of Infusion Reactions: Prophylaxis Pre-Medications, Post-Infusion Management, and Treatment Recommendations for Grade 1, 2, 3, 4 Symptoms  see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Taken within 20 minutes pre-infusion and 30 (±10) minutes of infusion completion
		  	MEASURE WEIGHT	Interval: --	Occurrences: --		  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	Physical Exam + ECOG
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	ABSOLUTE NEUTROPHIL COUNT	Interval: --	Occurrences: --		  	ABSOLUTE LYMPHOCYTE COUNT	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --			Labs
  	BILIRUBIN DIRECT	Interval: --	Occurrences: --			Labs
  	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --			Labs
  	CANCER ANTIGEN 125	Interval: --	Occurrences: --		  	CANCER ANTIGEN 15-3	Interval: --	Occurrences: --		  	MISCELLANEOUS REFERRAL TEST	Interval: --	Occurrences: --	Comments:	Cancer antigen 27-29 (CA-BR)
		  	CARCINOEMBRYONIC ANTIGEN (CEA)	Interval: --	Occurrences: --			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Nursing Orders
  	TREATMENT CONDITIONS 13	Interval: --	Occurrences: --	Comments:	HOLD and notify provider if 
o ANC LESS than 1000; 
o Platelets LESS than 100,000; 
o AST or ALT GREATER than 3 times ULN or total bilirubin GREATER than 1.5 times ULN; 
o Serum creatinine GREATER than 1.5x ULN or 1.5x ABOVE baseline.
			Provider Communication
  	ONC PROVIDER COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Dose adjustment allowed: 
Level 1: 6 mg/kg; 
Level 2: 3 mg/kg; 
Adjustment from 10 to 3 mg/kg is allowed. 
			Chemotherapy
  	INV-ONC-392 (ONC-392-001/Pro00033015/Chang) 6 mg/kg in dextrose 5% 500 mL	Dose: 6 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose			Offset: 30 Minutes	Instructions:	Administer intravenously using 0.2 micron inline filter over 90 minutes for initial infusion, then over 60 minutes for subsequent infusions. After the infusion, flush by adding 25mL of 0.9% NaCl to the IV bag to ensure all drug is infused. Prepared bag/syringe is stable for 4 hours at room temperature. 
Final concentration can be between 0.5mg/mL to 3mg/mL. 
HAZARDOUS - Handle with care
Caution: New Drug-Limited by Federal (USA) Law to Investigational use.

	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ONC-392 30 MG/ML INTRAVENOUS SOLN (ONC-392-001/PRO00033015/CHANG)	Medications	6 mg/kg	Main Ingredient	Yes	DEXTROSE 5 % IN WATER (D5W) INTRAVENOUS SOLUTION	QS Base	500 mL	Yes	Yes				Post-Hydration
  	sodium chloride 0.9 % infusion	Dose: --	Route: intravenous	continuous	Start: S					Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Post-infusion observation time is minimum 30 minutes (±10 minutes)
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
6. Notify the treating physician.
7. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
8. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain) 
1. Stop the infusion. 
2. Notify the CERT team and treating physician immediately. 
3. Place the patient on continuous monitoring. 
4. Obtain vital signs. 
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%. 
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing. 
7. Administer diphenhydramine 50 mg intravenous once and acetaminophen 650 mg once. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg  orally and Famotidine 20 mg intravenous once. 
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe). 
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician. 
10. If the infusion is interrupted, then restart the infusion at 50% of the original infusion rate when symptoms resolve.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 - SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise - cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg,  confusion, collapse, loss of consciousness, or incontinence) 
1. Stop the infusion. 
2. Notify the CERT team and treating physician immediately. 
3. Place the patient on continuous monitoring. 
4. Obtain vital signs. 
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position. 
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%. 
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing. 
8. Administer diphenhydramine 50 mg intravenous once and methylprednisolone 100 mg. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg  orally and Famotidine 20 mg intravenous once. 
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous. 
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 8	Interval: --	Occurrences: --	Comments:	Grade 4 Infusion Reaction: life-threatening; pressor or ventilator support indicated. See Emergency Medications. 
		  	ONC NURSING COMMUNICATION 9	Interval: --	Occurrences: --	Comments:	Treatment and safety management decisions all to be based upon local laboratory data.  Protocol does not provide reference ranges.
		  	sodium chloride 0.9 % infusion	Dose: 50-100 mL/hr	Route: intravenous	PRN	Start: S				  	sodium chloride 0.9 % infusion	Dose: 1,000 mL	Route: intravenous	PRN	Start: S				  	acetaminophen (TYLENOL) tablet 650 mg	Dose: 650 mg	Route: oral	PRN	Start: S				  	diphenhydrAMINE (BENADRYL) injection 50 mg	Dose: 50 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	methylPREDNISolone sodium succinate (Solu-MEDROL) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN	Start: S				  	epINEPHrine (ADRENALIN) injection 1 mg/mL 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 15	Repeat 1 time	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	ONC INFUSION APPOINTMENT REQUEST 5	Interval: --	Occurrences: --			Line Flush
  	sodium chloride 0.9% flush 25 mL	Dose: 25 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Please refer to Protocol Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: see 1.10.3 Study Schedule in Part C: Table 4: Study Schedule for Expansion Cohorts Part C Arm B. see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
		  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	Please refer to Section 7.9 Immune-mediated Adverse Reaction (IMAR) Management Plan and Table 12: Dose Modifications for IMARS: see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
		  	ONC NURSING COMMUNICATION 6	Interval: --	Occurrences: --	Comments:	Please refer to Protocol Section 7.10 Prophylactic and Acute Management of Infusion Reactions: Prophylaxis Pre-Medications, Post-Infusion Management, and Treatment Recommendations for Grade 1, 2, 3, 4 Symptoms  see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Taken within 20 minutes pre-infusion and 30 (±10) minutes of infusion completion
		  	MEASURE WEIGHT	Interval: --	Occurrences: --		  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	Physical Exam + ECOG
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	ABSOLUTE NEUTROPHIL COUNT	Interval: --	Occurrences: --		  	ABSOLUTE LYMPHOCYTE COUNT	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --			Labs
  	BILIRUBIN DIRECT	Interval: --	Occurrences: --			Labs
  	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --			Labs
  	CANCER ANTIGEN 125	Interval: --	Occurrences: --		  	CANCER ANTIGEN 15-3	Interval: --	Occurrences: --		  	MISCELLANEOUS REFERRAL TEST	Interval: --	Occurrences: --	Comments:	Cancer antigen 27-29 (CA-BR)
		  	CARCINOEMBRYONIC ANTIGEN (CEA)	Interval: --	Occurrences: --			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Nursing Orders
  	TREATMENT CONDITIONS 13	Interval: --	Occurrences: --	Comments:	HOLD and notify provider if 
o ANC LESS than 1000; 
o Platelets LESS than 100,000; 
o AST or ALT GREATER than 3 times ULN or total bilirubin GREATER than 1.5 times ULN; 
o Serum creatinine GREATER than 1.5x ULN or 1.5x ABOVE baseline.
			Provider Communication
  	ONC PROVIDER COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Dose adjustment allowed: 
Level 1: 6 mg/kg; 
Level 2: 3 mg/kg; 
Adjustment from 10 to 3 mg/kg is allowed. 
			Chemotherapy
  	INV-ONC-392 (ONC-392-001/Pro00033015/Chang) 6 mg/kg in dextrose 5% 500 mL	Dose: 6 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose			Offset: 30 Minutes	Instructions:	Administer intravenously using 0.2 micron inline filter over 90 minutes for initial infusion, then over 60 minutes for subsequent infusions. After the infusion, flush by adding 25mL of 0.9% NaCl to the IV bag to ensure all drug is infused. Prepared bag/syringe is stable for 4 hours at room temperature. 
Final concentration can be between 0.5mg/mL to 3mg/mL. 
HAZARDOUS - Handle with care
Caution: New Drug-Limited by Federal (USA) Law to Investigational use.

	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ONC-392 30 MG/ML INTRAVENOUS SOLN (ONC-392-001/PRO00033015/CHANG)	Medications	6 mg/kg	Main Ingredient	Yes	DEXTROSE 5 % IN WATER (D5W) INTRAVENOUS SOLUTION	QS Base	500 mL	Yes	Yes				Post-Hydration
  	sodium chloride 0.9 % infusion	Dose: --	Route: intravenous	continuous	Start: S					Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Post-infusion observation time is minimum 30 minutes (±10 minutes)
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
6. Notify the treating physician.
7. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
8. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain) 
1. Stop the infusion. 
2. Notify the CERT team and treating physician immediately. 
3. Place the patient on continuous monitoring. 
4. Obtain vital signs. 
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%. 
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing. 
7. Administer diphenhydramine 50 mg intravenous once and acetaminophen 650 mg once. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg  orally and Famotidine 20 mg intravenous once. 
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe). 
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician. 
10. If the infusion is interrupted, then restart the infusion at 50% of the original infusion rate when symptoms resolve.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 - SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise - cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg,  confusion, collapse, loss of consciousness, or incontinence) 
1. Stop the infusion. 
2. Notify the CERT team and treating physician immediately. 
3. Place the patient on continuous monitoring. 
4. Obtain vital signs. 
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position. 
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%. 
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing. 
8. Administer diphenhydramine 50 mg intravenous once and methylprednisolone 100 mg. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg  orally and Famotidine 20 mg intravenous once. 
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous. 
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 8	Interval: --	Occurrences: --	Comments:	Grade 4 Infusion Reaction: life-threatening; pressor or ventilator support indicated. See Emergency Medications. 
		  	ONC NURSING COMMUNICATION 9	Interval: --	Occurrences: --	Comments:	Treatment and safety management decisions all to be based upon local laboratory data.  Protocol does not provide reference ranges.
		  	sodium chloride 0.9 % infusion	Dose: 50-100 mL/hr	Route: intravenous	PRN	Start: S				  	sodium chloride 0.9 % infusion	Dose: 1,000 mL	Route: intravenous	PRN	Start: S				  	acetaminophen (TYLENOL) tablet 650 mg	Dose: 650 mg	Route: oral	PRN	Start: S				  	diphenhydrAMINE (BENADRYL) injection 50 mg	Dose: 50 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	methylPREDNISolone sodium succinate (Solu-MEDROL) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN	Start: S				  	epINEPHrine (ADRENALIN) injection 1 mg/mL 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled				Day 8	Perform every 1 day x1		Imaging
  	CT CHEST W CONTRAST ABDOMEN W CONTRAST PELVIS W CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI with preference for CT. If MRI is needed, please order as appropriate.
					
Cycle 16	Repeat 1 time	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	ONC INFUSION APPOINTMENT REQUEST 5	Interval: --	Occurrences: --			Line Flush
  	sodium chloride 0.9% flush 25 mL	Dose: 25 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Please refer to Protocol Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: see 1.10.3 Study Schedule in Part C: Table 4: Study Schedule for Expansion Cohorts Part C Arm B. see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
		  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	Please refer to Section 7.9 Immune-mediated Adverse Reaction (IMAR) Management Plan and Table 12: Dose Modifications for IMARS: see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
		  	ONC NURSING COMMUNICATION 6	Interval: --	Occurrences: --	Comments:	Please refer to Protocol Section 7.10 Prophylactic and Acute Management of Infusion Reactions: Prophylaxis Pre-Medications, Post-Infusion Management, and Treatment Recommendations for Grade 1, 2, 3, 4 Symptoms  see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Taken within 20 minutes pre-infusion and 30 (±10) minutes of infusion completion
		  	MEASURE WEIGHT	Interval: --	Occurrences: --		  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	Physical Exam + ECOG
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	ABSOLUTE NEUTROPHIL COUNT	Interval: --	Occurrences: --		  	ABSOLUTE LYMPHOCYTE COUNT	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --			Labs
  	BILIRUBIN DIRECT	Interval: --	Occurrences: --			Labs
  	LDH	Interval: --	Occurrences: --			Labs
  	THYROID STIMULATING HORMONE	Interval: --	Occurrences: --		  	T3	Interval: --	Occurrences: --		  	T4, FREE	Interval: --	Occurrences: --			Labs
  	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --			Labs
  	CANCER ANTIGEN 125	Interval: --	Occurrences: --		  	CANCER ANTIGEN 15-3	Interval: --	Occurrences: --		  	MISCELLANEOUS REFERRAL TEST	Interval: --	Occurrences: --	Comments:	Cancer antigen 27-29 (CA-BR)
		  	CARCINOEMBRYONIC ANTIGEN (CEA)	Interval: --	Occurrences: --			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Nursing Orders
  	TREATMENT CONDITIONS 13	Interval: --	Occurrences: --	Comments:	HOLD and notify provider if 
o ANC LESS than 1000; 
o Platelets LESS than 100,000; 
o AST or ALT GREATER than 3 times ULN or total bilirubin GREATER than 1.5 times ULN; 
o Serum creatinine GREATER than 1.5x ULN or 1.5x ABOVE baseline.
			Provider Communication
  	ONC PROVIDER COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Dose adjustment allowed: 
Level 1: 6 mg/kg; 
Level 2: 3 mg/kg; 
Adjustment from 10 to 3 mg/kg is allowed. 
			Chemotherapy
  	INV-ONC-392 (ONC-392-001/Pro00033015/Chang) 6 mg/kg in dextrose 5% 500 mL	Dose: 6 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose			Offset: 30 Minutes	Instructions:	Administer intravenously using 0.2 micron inline filter over 90 minutes for initial infusion, then over 60 minutes for subsequent infusions. After the infusion, flush by adding 25mL of 0.9% NaCl to the IV bag to ensure all drug is infused. Prepared bag/syringe is stable for 4 hours at room temperature. 
Final concentration can be between 0.5mg/mL to 3mg/mL. 
HAZARDOUS - Handle with care
Caution: New Drug-Limited by Federal (USA) Law to Investigational use.

	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ONC-392 30 MG/ML INTRAVENOUS SOLN (ONC-392-001/PRO00033015/CHANG)	Medications	6 mg/kg	Main Ingredient	Yes	DEXTROSE 5 % IN WATER (D5W) INTRAVENOUS SOLUTION	QS Base	500 mL	Yes	Yes				Post-Hydration
  	sodium chloride 0.9 % infusion	Dose: --	Route: intravenous	continuous	Start: S					Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Post-infusion observation time is minimum 30 minutes (±10 minutes)
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
6. Notify the treating physician.
7. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
8. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain) 
1. Stop the infusion. 
2. Notify the CERT team and treating physician immediately. 
3. Place the patient on continuous monitoring. 
4. Obtain vital signs. 
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%. 
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing. 
7. Administer diphenhydramine 50 mg intravenous once and acetaminophen 650 mg once. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg  orally and Famotidine 20 mg intravenous once. 
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe). 
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician. 
10. If the infusion is interrupted, then restart the infusion at 50% of the original infusion rate when symptoms resolve.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 - SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise - cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg,  confusion, collapse, loss of consciousness, or incontinence) 
1. Stop the infusion. 
2. Notify the CERT team and treating physician immediately. 
3. Place the patient on continuous monitoring. 
4. Obtain vital signs. 
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position. 
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%. 
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing. 
8. Administer diphenhydramine 50 mg intravenous once and methylprednisolone 100 mg. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg  orally and Famotidine 20 mg intravenous once. 
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous. 
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 8	Interval: --	Occurrences: --	Comments:	Grade 4 Infusion Reaction: life-threatening; pressor or ventilator support indicated. See Emergency Medications. 
		  	ONC NURSING COMMUNICATION 9	Interval: --	Occurrences: --	Comments:	Treatment and safety management decisions all to be based upon local laboratory data.  Protocol does not provide reference ranges.
		  	sodium chloride 0.9 % infusion	Dose: 50-100 mL/hr	Route: intravenous	PRN	Start: S				  	sodium chloride 0.9 % infusion	Dose: 1,000 mL	Route: intravenous	PRN	Start: S				  	acetaminophen (TYLENOL) tablet 650 mg	Dose: 650 mg	Route: oral	PRN	Start: S				  	diphenhydrAMINE (BENADRYL) injection 50 mg	Dose: 50 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	methylPREDNISolone sodium succinate (Solu-MEDROL) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN	Start: S				  	epINEPHrine (ADRENALIN) injection 1 mg/mL 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 17	Repeat 1 time	Cycle length: 30 days	Day 1	Perform every 1 day x1		Appointment Requests
  	ONC INFUSION APPOINTMENT REQUEST 5	Interval: --	Occurrences: --			Line Flush
  	sodium chloride 0.9% flush 25 mL	Dose: 25 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Please refer to Protocol Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: see 1.10.3 Study Schedule in Part C: Table 4: Study Schedule for Expansion Cohorts Part C Arm B. see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
		  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	Please refer to Section 7.9 Immune-mediated Adverse Reaction (IMAR) Management Plan and Table 12: Dose Modifications for IMARS: see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
		  	ONC NURSING COMMUNICATION 6	Interval: --	Occurrences: --	Comments:	Please refer to Protocol Section 7.10 Prophylactic and Acute Management of Infusion Reactions: Prophylaxis Pre-Medications, Post-Infusion Management, and Treatment Recommendations for Grade 1, 2, 3, 4 Symptoms  see Protocol Hyperlink: ONC-392-001_Protocol_V3.0_30May2022_Clean.pdf.
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Taken within 20 minutes pre-infusion and 30 (±10) minutes of infusion completion
		  	MEASURE WEIGHT	Interval: --	Occurrences: --		  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	Physical Exam + ECOG
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	ABSOLUTE NEUTROPHIL COUNT	Interval: --	Occurrences: --		  	ABSOLUTE LYMPHOCYTE COUNT	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --			Labs
  	BILIRUBIN DIRECT	Interval: --	Occurrences: --			Labs
  	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --			Labs
  	CANCER ANTIGEN 125	Interval: --	Occurrences: --		  	CANCER ANTIGEN 15-3	Interval: --	Occurrences: --		  	MISCELLANEOUS REFERRAL TEST	Interval: --	Occurrences: --	Comments:	Cancer antigen 27-29 (CA-BR)
		  	CARCINOEMBRYONIC ANTIGEN (CEA)	Interval: --	Occurrences: --			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Nursing Orders
  	TREATMENT CONDITIONS 13	Interval: --	Occurrences: --	Comments:	HOLD and notify provider if 
o ANC LESS than 1000; 
o Platelets LESS than 100,000; 
o AST or ALT GREATER than 3 times ULN or total bilirubin GREATER than 1.5 times ULN; 
o Serum creatinine GREATER than 1.5x ULN or 1.5x ABOVE baseline.
			Provider Communication
  	ONC PROVIDER COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Dose adjustment allowed: 
Level 1: 6 mg/kg; 
Level 2: 3 mg/kg; 
Adjustment from 10 to 3 mg/kg is allowed. 
			Chemotherapy
  	INV-ONC-392 (ONC-392-001/Pro00033015/Chang) 6 mg/kg in dextrose 5% 500 mL	Dose: 6 mg/kg	Route: intravenous	once over 90 Minutes for 1 dose			Offset: 30 Minutes	Instructions:	Administer intravenously using 0.2 micron inline filter over 90 minutes for initial infusion, then over 60 minutes for subsequent infusions. After the infusion, flush by adding 25mL of 0.9% NaCl to the IV bag to ensure all drug is infused. Prepared bag/syringe is stable for 4 hours at room temperature. 
Final concentration can be between 0.5mg/mL to 3mg/mL. 
HAZARDOUS - Handle with care
Caution: New Drug-Limited by Federal (USA) Law to Investigational use.

	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	INV-ONC-392 30 MG/ML INTRAVENOUS SOLN (ONC-392-001/PRO00033015/CHANG)	Medications	6 mg/kg	Main Ingredient	Yes	DEXTROSE 5 % IN WATER (D5W) INTRAVENOUS SOLUTION	QS Base	500 mL	Yes	Yes				Post-Hydration
  	sodium chloride 0.9 % infusion	Dose: --	Route: intravenous	continuous	Start: S					Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Post-infusion observation time is minimum 30 minutes (±10 minutes)
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
6. Notify the treating physician.
7. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
8. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain) 
1. Stop the infusion. 
2. Notify the CERT team and treating physician immediately. 
3. Place the patient on continuous monitoring. 
4. Obtain vital signs. 
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%. 
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing. 
7. Administer diphenhydramine 50 mg intravenous once and acetaminophen 650 mg once. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg  orally and Famotidine 20 mg intravenous once. 
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe). 
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician. 
10. If the infusion is interrupted, then restart the infusion at 50% of the original infusion rate when symptoms resolve.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 - SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise - cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg,  confusion, collapse, loss of consciousness, or incontinence) 
1. Stop the infusion. 
2. Notify the CERT team and treating physician immediately. 
3. Place the patient on continuous monitoring. 
4. Obtain vital signs. 
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position. 
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%. 
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing. 
8. Administer diphenhydramine 50 mg intravenous once and methylprednisolone 100 mg. If less than 30 minutes since the last dose of Diphenhydramine, administer Fexofenadine 180 mg  orally and Famotidine 20 mg intravenous once. 
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous. 
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 8	Interval: --	Occurrences: --	Comments:	Grade 4 Infusion Reaction: life-threatening; pressor or ventilator support indicated. See Emergency Medications. 
		  	ONC NURSING COMMUNICATION 9	Interval: --	Occurrences: --	Comments:	Treatment and safety management decisions all to be based upon local laboratory data.  Protocol does not provide reference ranges.
		  	sodium chloride 0.9 % infusion	Dose: 50-100 mL/hr	Route: intravenous	PRN	Start: S				  	sodium chloride 0.9 % infusion	Dose: 1,000 mL	Route: intravenous	PRN	Start: S				  	acetaminophen (TYLENOL) tablet 650 mg	Dose: 650 mg	Route: oral	PRN	Start: S				  	diphenhydrAMINE (BENADRYL) injection 50 mg	Dose: 50 mg	Route: intravenous	PRN	Start: S				  	fexofenadine (ALLEGRA) tablet 180 mg	Dose: 180 mg	Route: oral	PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	methylPREDNISolone sodium succinate (Solu-MEDROL) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN	Start: S				  	epINEPHrine (ADRENALIN) injection 1 mg/mL 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
EOT	Repeat 1 time	Cycle length: 30 days	Day 1	Perform every 1 day x1		Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --		  	MEASURE WEIGHT	Interval: --	Occurrences: --		  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	Physical Exam + ECOG
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	ABSOLUTE NEUTROPHIL COUNT	Interval: --	Occurrences: --		  	ABSOLUTE LYMPHOCYTE COUNT	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --			Labs
  	BILIRUBIN DIRECT	Interval: --	Occurrences: --			Labs
  	LDH	Interval: --	Occurrences: --			Labs
  	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		  	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --			Labs
  	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --			Labs
☐	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --		☐	HCG QUANTITATIVE, SERUM	Interval: --	Occurrences: --		☐	HCG QUALITATIVE, URINE SCREEN	Interval: --	Occurrences: --			Labs
  	THYROID STIMULATING HORMONE	Interval: --	Occurrences: --		  	T3	Interval: --	Occurrences: --		  	T4, FREE	Interval: --	Occurrences: --			Labs
  	CANCER ANTIGEN 125	Interval: --	Occurrences: --		  	CANCER ANTIGEN 15-3	Interval: --	Occurrences: --		  	MISCELLANEOUS REFERRAL TEST	Interval: --	Occurrences: --	Comments:	Cancer antigen 27-29 (CA-BR)
		  	CARCINOEMBRYONIC ANTIGEN (CEA)	Interval: --	Occurrences: --			Imaging
  	CT CHEST W CONTRAST ABDOMEN W CONTRAST PELVIS W CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI with preference for CT. If MRI is needed, please order as appropriate.
			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --					
Survival Follow-up	Repeat 1 time	Cycle length: 1 day	Day 1	Perform every 1 day x1		Provider Communication
  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Tumor Imaging: 
o If a patient discontinues study treatment for reasons other than disease progression, the patient should be followed for PFS with imaging every three months (±2 weeks) through 12 months after the first dose of study drug.  
o Please order imaging as appropriate.
		  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Survival Assessment to be done quarterly.