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OP RSH PRO00040158 PRATH A032201 ARM 2	

Types:      Research Oncology Treatment
Synonyms:  A032201, PRATH, PRO00040158, KEYTRUDA, TIVOZANIB

Cycle 1	Repeat 1 time	Cycle length: 84 days	C1 D1	Perform every 1 day x1			Research tolerance: -0/+0 days	Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Nursing  Communication: Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink:   A032201_Prath
		  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for TIVOZANIB Treatment: Refer to Section 10.2[RA1]   Management of AEs Associated with Refer to section  8.2
Protocol Access Hyperlink:  A032201_Prath
			Nursing Orders
  	ONC NURSING COMMUNICATION 116	Interval: --	Occurrences: --	Comments:	Medical history
			Nursing Orders
  	ONC NURSING COMMUNICATION 75	Interval: --	Occurrences: --	Comments:	Physical Exam

Physical examination and staging scans are required every 16w (+/-2w) for year 1 and 2 after registration; then every 24w (+/-3w)until 5 years from registration or until disease progression, or consent withdrawal, whichever comes first; thereafter, survival information is required every 12 months(+/-2 months) until 10 years from registration.
			Nursing Orders
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Concomitant medications
			Nursing Orders
  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	Adverse Events
			Nursing Orders
  	ONC NURSING COMMUNICATION 71	Interval: --	Occurrences: --	Comments:	Pill compliance must be documented by any member of the care team. If the sample diary in Appendix II or III is used, it should begin the day the patient starts taking medication and should be completed per protocol and returned to the treating institution.
			Imaging
◯	CT HEAD W CONTRAST	Interval: --	Occurrences: --	Comments:	MRI or CT
		◯	CT HEAD W WO CONTRAST	Interval: --	Occurrences: --	Comments:	MRI or CT
		◯	CT HEAD WO CONTRAST	Interval: --	Occurrences: --	Comments:	MRI or CT
		◉	MRI BRAIN W WO CONTRAST	Interval: --	Occurrences: --	Comments:	MRI or CT
		◯	MRI BRAIN W CONTRAST	Interval: --	Occurrences: --	Comments:	MRI or CT
		◯	MRI BRAIN WO CONTRAST	Interval: --	Occurrences: --	Comments:	MRI or CT
			Imaging
☑	CT CHEST W WO CONTRAST ABDOMEN W CONTRAST PELVIS W CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI 

CT pelvis is as clinically indicated . Imaging scans (with or without contrast) will be obtained prior to registration and then every 12 weeks +/- 2 weeks during the first year, and then every 16 weeks, +/- 3 weeks for second year, every 24 weeks +/- 3 weeks for 3 years , then annually +/-4 weeks until 5 years after registration or progression , whichever comes first. Imaging beyond 5 years is recommended as clinically indicated .
		☐	MRI CHEST W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI 

CT pelvis is as clinically indicated . Imaging scans (with or without contrast) will be obtained prior to registration and then every 12 weeks +/- 2 weeks during the first year, and then every 16 weeks, +/- 3 weeks for second year, every 24 weeks +/- 3 weeks for 3 years , then annually +/-4 weeks until 5 years after registration or progression , whichever comes first. Imaging beyond 5 years is recommended as clinically indicated .
		☐	MRI ABDOMEN W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI

CT pelvis is as clinically indicated . Imaging scans (with or without contrast) will be obtained prior to registration and then every 12 weeks +/- 2 weeks during the first year, and then every 16 weeks, +/- 3 weeks for second year, every 24 weeks +/- 3 weeks for 3 years , then annually +/-4 weeks until 5 years after registration or progression , whichever comes first. Imaging beyond 5 years is recommended as clinically indicated .
		☐	MRI PELVIS W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI 

CT pelvis is as clinically indicated . Imaging scans (with or without contrast) will be obtained prior to registration and then every 12 weeks +/- 2 weeks during the first year, and then every 16 weeks, +/- 3 weeks for second year, every 24 weeks +/- 3 weeks for 3 years , then annually +/-4 weeks until 5 years after registration or progression , whichever comes first. Imaging beyond 5 years is recommended as clinically indicated .
			Nursing Orders
  	ONC NURSING COMMUNICATION 72	Interval: --	Occurrences: --	Comments:	FSKI-19/PROMIS-Fatigue/EQ-5D-5L

For patients registered to A032201-HO1

Year 1 : Every 12w ; Year 2: every 16w, Year 3-5: every 24w
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Blood pressure, body temperature, heart rate
		  	RESEARCH - MEASURE WEIGHT	Interval: --	Occurrences: --			Cardiology
  	ECG 12-LEAD	Interval: --	Occurrences: --			Labs
  	ONC NURSING COMMUNICATION 52	Interval: --	Occurrences: --	Comments:	Labs completed prior to registration may be used for C1D1 test if obtained <= 3 days prior to treatment
			Labs
☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		☑	MAGNESIUM LEVEL	Interval: --	Occurrences: --			Labs
  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	CALCIUM LEVEL	Interval: --	Occurrences: --			Labs
  	THYROID STIMULATING HORMONE	Interval: --	Occurrences: --			Labs
  	CORTISOL LEVEL, AM	Interval: --	Occurrences: --	Comments:	Must be collected in the morning.
			Labs
  	CREATININE CLEARANCE, URINE, 24 HOUR	Interval: --	Occurrences: --			Labs
☐	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
		☐	HCG QUANTITATIVE, SERUM	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
		☑	HCG QUALITATIVE, URINE SCREEN	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
			Labs
◉	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	All patients will have urinalysis or UPCR performed at screening; if urine protein is >=2+, 24-hour urine collection or UPC ratio will be required . If UPCR <2, optimize blood pressure and manage per institutional guidelines .
		◯	URINE PROTEIN/CREATININE RATIO, RANDOM	Interval: --	Occurrences: --	Comments:	All patients will have urinalysis or UPCR performed at screening; if urine protein is >=2+, 24-hour urine collection or UPC ratio will be required . If UPCR <2, optimize blood pressure and manage per institutional guidelines .
			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	C1D1,PTFU, PROGRESSION

PTFU ( 6,12,18,24 months from C1D1)
			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	C1D1,PTFU, PROGRESSION

PTFU ( 6,12,18,24 months from C1D1)
			Chemotherapy
  	ONC NURSING COMMUNICATION 70	Interval: --	Occurrences: --	Comments:	Tivozanib pills will be ordered directly from IDS pharmacy via paper Rx order form
		  	ONC NURSING COMMUNICATION 69	Interval: --	Occurrences: --	Comments:	Tivozanib 1.34 mg once daily on days 1 through 21 of a 28-day cycle.
Take with or without food.
Swallow the tivozanib capsule whole with a glass of water; Do not open the capsule.
Wound healing may be impaired. Administration should be stooped prior to surgery.
Multiple drug-drug or drug-food interactions. Review patient medical profile.
			Oral Chemotherapy
  	ONC NURSING COMMUNICATION 67	Interval: --	Occurrences: --	Comments:	Assess compliance to Tivozanib
		  	ONC NURSING COMMUNICATION 72	Interval: --	Occurrences: --	Comments:	Dose modification and management of Tivozanib treatment: refer to section 8.2.1 of protocol
			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.
			Line Care
  	INSERT PERIPHERAL IV OR ACCESS PORTACATH	Interval: --	Occurrences: --		  	sodium chloride 0.9% flush 20 mL	Dose: 20 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.			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Dose modification and management of Pembrolizumab treatment: refer to section 8.3 of protocol
			Immuno-therapy
  	pembrolizumab (KEYTRUDA) 400 mg in sodium chloride 0.9% 100 mL IVPB	Dose: 400 mg	Route: intravenous	once over 30 Minutes for 1 dose	Start: S			Instructions:	Administer with low protein binding 0.22 micron in-line filter. Do not shake. Do not mix with other medications.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	PEMBROLIZUMAB 25 MG/ML INTRAVENOUS SOLUTION	Medications	400 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	84 mL	Yes	Yes				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.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 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 Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 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.
		  	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 Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) 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.
		  	acetaminophen (TYLENOL) tablet 650 mg	Dose: 650 mg	Route: oral	once PRN	Start: S				  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 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				C1 D29	Perform every 1 day x1			Research tolerance: -0/+0 days	Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Nursing  Communication: Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink:   A032201_Prath
		  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for TIVOZANIB Treatment: Refer to Section 10.2[RA1]   Management of AEs Associated with Refer to section  8.2
Protocol Access Hyperlink:  A032201_Prath
			Nursing Orders
  	ONC NURSING COMMUNICATION 116	Interval: --	Occurrences: --	Comments:	Medical history
			Nursing Orders
  	ONC NURSING COMMUNICATION 75	Interval: --	Occurrences: --	Comments:	Physical Exam

Physical examination and staging scans are required every 16w (+/-2w) for year 1 and 2 after registration; then every 24w (+/-3w)until 5 years from registration or until disease progression, or consent withdrawal, whichever comes first; thereafter, survival information is required every 12 months(+/-2 months) until 10 years from registration.
			Nursing Orders
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Concomitant medications
			Nursing Orders
  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	Adverse Events
			Nursing Orders
  	ONC NURSING COMMUNICATION 71	Interval: --	Occurrences: --	Comments:	Pill compliance must be documented by any member of the care team. If the sample diary in Appendix II or III is used, it should begin the day the patient starts taking medication and should be completed per protocol and returned to the treating institution.
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Blood pressure, body temperature, heart rate
		  	RESEARCH - MEASURE WEIGHT	Interval: --	Occurrences: --			Cardiology
  	ECG 12-LEAD	Interval: --	Occurrences: --			Labs
☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		☑	MAGNESIUM LEVEL	Interval: --	Occurrences: --			Labs
  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	CALCIUM LEVEL	Interval: --	Occurrences: --			Labs
  	CORTISOL LEVEL, AM	Interval: --	Occurrences: --	Comments:	Must be collected in the morning.
			Labs
  	CREATININE CLEARANCE, URINE, 24 HOUR	Interval: --	Occurrences: --			Labs
☐	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
		☐	HCG QUANTITATIVE, SERUM	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
		☑	HCG QUALITATIVE, URINE SCREEN	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
			Labs
◉	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	All patients will have urinalysis or UPCR performed at screening; if urine protein is >=2+, 24-hour urine collection or UPC ratio will be required . If UPCR <2, optimize blood pressure and manage per institutional guidelines .
		◯	URINE PROTEIN/CREATININE RATIO, RANDOM	Interval: --	Occurrences: --	Comments:	All patients will have urinalysis or UPCR performed at screening; if urine protein is >=2+, 24-hour urine collection or UPC ratio will be required . If UPCR <2, optimize blood pressure and manage per institutional guidelines .
			Chemotherapy
  	ONC NURSING COMMUNICATION 70	Interval: --	Occurrences: --	Comments:	Tivozanib pills will be ordered directly from IDS pharmacy via paper Rx order form
		  	ONC NURSING COMMUNICATION 69	Interval: --	Occurrences: --	Comments:	Tivozanib 1.34 mg once daily on days 1 through 21 of a 28-day cycle.
Take with or without food.
Swallow the tivozanib capsule whole with a glass of water; Do not open the capsule.
Wound healing may be impaired. Administration should be stooped prior to surgery.
Multiple drug-drug or drug-food interactions. Review patient medical profile.
			Oral Chemotherapy
  	ONC NURSING COMMUNICATION 67	Interval: --	Occurrences: --	Comments:	Assess compliance to Tivozanib
		  	ONC NURSING COMMUNICATION 72	Interval: --	Occurrences: --	Comments:	Dose modification and management of Tivozanib treatment: refer to section 8.2.1 of protocol
				C1 D43	Perform every 1 day x1			Research tolerance: -0/+0 days	Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Nursing  Communication: Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink:   A032201_Prath
		  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for TIVOZANIB Treatment: Refer to Section 10.2[RA1]   Management of AEs Associated with Refer to section  8.2
Protocol Access Hyperlink:  A032201_Prath
			Nursing Orders
  	ONC NURSING COMMUNICATION 116	Interval: --	Occurrences: --	Comments:	Medical history
			Nursing Orders
  	ONC NURSING COMMUNICATION 75	Interval: --	Occurrences: --	Comments:	Physical Exam

Physical examination and staging scans are required every 16w (+/-2w) for year 1 and 2 after registration; then every 24w (+/-3w)until 5 years from registration or until disease progression, or consent withdrawal, whichever comes first; thereafter, survival information is required every 12 months(+/-2 months) until 10 years from registration.
			Nursing Orders
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Concomitant medications
			Nursing Orders
  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	Adverse Events
			Nursing Orders
  	ONC NURSING COMMUNICATION 71	Interval: --	Occurrences: --	Comments:	Pill compliance must be documented by any member of the care team. If the sample diary in Appendix II or III is used, it should begin the day the patient starts taking medication and should be completed per protocol and returned to the treating institution.
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Blood pressure, body temperature, heart rate
		  	RESEARCH - MEASURE WEIGHT	Interval: --	Occurrences: --			Cardiology
  	ECG 12-LEAD	Interval: --	Occurrences: --			Labs
  	ONC NURSING COMMUNICATION 52	Interval: --	Occurrences: --	Comments:	Labs completed prior to registration may be used for C1D1 test if obtained <= 3 days prior to treatment
			Labs
☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		☑	MAGNESIUM LEVEL	Interval: --	Occurrences: --			Labs
  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	CALCIUM LEVEL	Interval: --	Occurrences: --			Labs
  	THYROID STIMULATING HORMONE	Interval: --	Occurrences: --			Labs
  	CORTISOL LEVEL, AM	Interval: --	Occurrences: --	Comments:	Must be collected in the morning.
			Labs
  	CREATININE CLEARANCE, URINE, 24 HOUR	Interval: --	Occurrences: --			Labs
☐	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
		☐	HCG QUANTITATIVE, SERUM	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
		☑	HCG QUALITATIVE, URINE SCREEN	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
			Labs
◉	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	All patients will have urinalysis or UPCR performed at screening; if urine protein is >=2+, 24-hour urine collection or UPC ratio will be required . If UPCR <2, optimize blood pressure and manage per institutional guidelines .
		◯	URINE PROTEIN/CREATININE RATIO, RANDOM	Interval: --	Occurrences: --	Comments:	All patients will have urinalysis or UPCR performed at screening; if urine protein is >=2+, 24-hour urine collection or UPC ratio will be required . If UPCR <2, optimize blood pressure and manage per institutional guidelines .
			Chemotherapy
  	ONC NURSING COMMUNICATION 70	Interval: --	Occurrences: --	Comments:	Tivozanib pills will be ordered directly from IDS pharmacy via paper Rx order form
		  	ONC NURSING COMMUNICATION 69	Interval: --	Occurrences: --	Comments:	Tivozanib 1.34 mg once daily on days 1 through 21 of a 28-day cycle.
Take with or without food.
Swallow the tivozanib capsule whole with a glass of water; Do not open the capsule.
Wound healing may be impaired. Administration should be stooped prior to surgery.
Multiple drug-drug or drug-food interactions. Review patient medical profile.
			Oral Chemotherapy
  	ONC NURSING COMMUNICATION 67	Interval: --	Occurrences: --	Comments:	Assess compliance to Tivozanib
		  	ONC NURSING COMMUNICATION 72	Interval: --	Occurrences: --	Comments:	Dose modification and management of Tivozanib treatment: refer to section 8.2.1 of protocol
			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.
			Line Care
  	INSERT PERIPHERAL IV OR ACCESS PORTACATH	Interval: --	Occurrences: --		  	sodium chloride 0.9% flush 20 mL	Dose: 20 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.			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Dose modification and management of Pembrolizumab treatment: refer to section 8.3 of protocol
			Immuno-therapy
  	pembrolizumab (KEYTRUDA) 400 mg in sodium chloride 0.9% 100 mL IVPB	Dose: 400 mg	Route: intravenous	once over 30 Minutes for 1 dose	Start: S			Instructions:	Administer with low protein binding 0.22 micron in-line filter. Do not shake. Do not mix with other medications.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	PEMBROLIZUMAB 25 MG/ML INTRAVENOUS SOLUTION	Medications	400 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	84 mL	Yes	Yes				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.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 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 Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 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.
		  	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 Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) 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.
		  	acetaminophen (TYLENOL) tablet 650 mg	Dose: 650 mg	Route: oral	once PRN	Start: S				  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 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				C1 D57	Perform every 1 day x1			Research tolerance: -0/+0 days	Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Nursing  Communication: Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink:   A032201_Prath
		  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for TIVOZANIB Treatment: Refer to Section 10.2[RA1]   Management of AEs Associated with Refer to section  8.2
Protocol Access Hyperlink:  A032201_Prath
			Nursing Orders
  	ONC NURSING COMMUNICATION 116	Interval: --	Occurrences: --	Comments:	Medical history
			Nursing Orders
  	ONC NURSING COMMUNICATION 75	Interval: --	Occurrences: --	Comments:	Physical Exam

Physical examination and staging scans are required every 16w (+/-2w) for year 1 and 2 after registration; then every 24w (+/-3w)until 5 years from registration or until disease progression, or consent withdrawal, whichever comes first; thereafter, survival information is required every 12 months(+/-2 months) until 10 years from registration.
			Nursing Orders
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Concomitant medications
			Nursing Orders
  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	Adverse Events
			Nursing Orders
  	ONC NURSING COMMUNICATION 71	Interval: --	Occurrences: --	Comments:	Pill compliance must be documented by any member of the care team. If the sample diary in Appendix II or III is used, it should begin the day the patient starts taking medication and should be completed per protocol and returned to the treating institution.
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Blood pressure, body temperature, heart rate
		  	RESEARCH - MEASURE WEIGHT	Interval: --	Occurrences: --			Cardiology
  	ECG 12-LEAD	Interval: --	Occurrences: --			Labs
  	ONC NURSING COMMUNICATION 52	Interval: --	Occurrences: --	Comments:	Labs completed prior to registration may be used for C1D1 test if obtained <= 3 days prior to treatment
			Labs
☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		☑	MAGNESIUM LEVEL	Interval: --	Occurrences: --			Labs
  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	CALCIUM LEVEL	Interval: --	Occurrences: --			Labs
  	THYROID STIMULATING HORMONE	Interval: --	Occurrences: --			Labs
  	CORTISOL LEVEL, AM	Interval: --	Occurrences: --	Comments:	Must be collected in the morning.
			Labs
  	CREATININE CLEARANCE, URINE, 24 HOUR	Interval: --	Occurrences: --			Labs
☐	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
		☐	HCG QUANTITATIVE, SERUM	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
		☑	HCG QUALITATIVE, URINE SCREEN	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
			Labs
◉	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	All patients will have urinalysis or UPCR performed at screening; if urine protein is >=2+, 24-hour urine collection or UPC ratio will be required . If UPCR <2, optimize blood pressure and manage per institutional guidelines .
		◯	URINE PROTEIN/CREATININE RATIO, RANDOM	Interval: --	Occurrences: --	Comments:	All patients will have urinalysis or UPCR performed at screening; if urine protein is >=2+, 24-hour urine collection or UPC ratio will be required . If UPCR <2, optimize blood pressure and manage per institutional guidelines .
			Chemotherapy
  	ONC NURSING COMMUNICATION 70	Interval: --	Occurrences: --	Comments:	Tivozanib pills will be ordered directly from IDS pharmacy via paper Rx order form
		  	ONC NURSING COMMUNICATION 69	Interval: --	Occurrences: --	Comments:	Tivozanib 1.34 mg once daily on days 1 through 21 of a 28-day cycle.
Take with or without food.
Swallow the tivozanib capsule whole with a glass of water; Do not open the capsule.
Wound healing may be impaired. Administration should be stooped prior to surgery.
Multiple drug-drug or drug-food interactions. Review patient medical profile.
			Oral Chemotherapy
  	ONC NURSING COMMUNICATION 67	Interval: --	Occurrences: --	Comments:	Assess compliance to Tivozanib
		  	ONC NURSING COMMUNICATION 72	Interval: --	Occurrences: --	Comments:	Dose modification and management of Tivozanib treatment: refer to section 8.2.1 of protocol
					
Cycle 2	Repeat 1 time	Cycle length: 84 days	C2 D1	Perform every 1 day x1			Research tolerance: -0/+0 days	Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Nursing  Communication: Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink:   A032201_Prath
		  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for TIVOZANIB Treatment: Refer to Section 10.2[RA1]   Management of AEs Associated with Refer to section  8.2
Protocol Access Hyperlink:  A032201_Prath
			Nursing Orders
  	ONC NURSING COMMUNICATION 116	Interval: --	Occurrences: --	Comments:	Medical history
			Nursing Orders
  	ONC NURSING COMMUNICATION 75	Interval: --	Occurrences: --	Comments:	Physical Exam

Physical examination and staging scans are required every 16w (+/-2w) for year 1 and 2 after registration; then every 24w (+/-3w)until 5 years from registration or until disease progression, or consent withdrawal, whichever comes first; thereafter, survival information is required every 12 months(+/-2 months) until 10 years from registration.
			Nursing Orders
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Concomitant medications
			Nursing Orders
  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	Adverse Events
			Nursing Orders
  	ONC NURSING COMMUNICATION 71	Interval: --	Occurrences: --	Comments:	Pill compliance must be documented by any member of the care team. If the sample diary in Appendix II or III is used, it should begin the day the patient starts taking medication and should be completed per protocol and returned to the treating institution.
			Imaging
◯	CT HEAD W CONTRAST	Interval: --	Occurrences: --	Comments:	MRI or CT
		◯	CT HEAD W WO CONTRAST	Interval: --	Occurrences: --	Comments:	MRI or CT
		◯	CT HEAD WO CONTRAST	Interval: --	Occurrences: --	Comments:	MRI or CT
		◉	MRI BRAIN W WO CONTRAST	Interval: --	Occurrences: --	Comments:	MRI or CT
		◯	MRI BRAIN W CONTRAST	Interval: --	Occurrences: --	Comments:	MRI or CT
		◯	MRI BRAIN WO CONTRAST	Interval: --	Occurrences: --	Comments:	MRI or CT
			Imaging
☑	CT CHEST W WO CONTRAST ABDOMEN W CONTRAST PELVIS W CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI 

CT pelvis is as clinically indicated . Imaging scans (with or without contrast) will be obtained prior to registration and then every 12 weeks +/- 2 weeks during the first year, and then every 16 weeks, +/- 3 weeks for second year, every 24 weeks +/- 3 weeks for 3 years , then annually +/-4 weeks until 5 years after registration or progression , whichever comes first. Imaging beyond 5 years is recommended as clinically indicated .
		☐	MRI CHEST W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI 

CT pelvis is as clinically indicated . Imaging scans (with or without contrast) will be obtained prior to registration and then every 12 weeks +/- 2 weeks during the first year, and then every 16 weeks, +/- 3 weeks for second year, every 24 weeks +/- 3 weeks for 3 years , then annually +/-4 weeks until 5 years after registration or progression , whichever comes first. Imaging beyond 5 years is recommended as clinically indicated .
		☐	MRI ABDOMEN W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI

CT pelvis is as clinically indicated . Imaging scans (with or without contrast) will be obtained prior to registration and then every 12 weeks +/- 2 weeks during the first year, and then every 16 weeks, +/- 3 weeks for second year, every 24 weeks +/- 3 weeks for 3 years , then annually +/-4 weeks until 5 years after registration or progression , whichever comes first. Imaging beyond 5 years is recommended as clinically indicated .
		☐	MRI PELVIS W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI 

CT pelvis is as clinically indicated . Imaging scans (with or without contrast) will be obtained prior to registration and then every 12 weeks +/- 2 weeks during the first year, and then every 16 weeks, +/- 3 weeks for second year, every 24 weeks +/- 3 weeks for 3 years , then annually +/-4 weeks until 5 years after registration or progression , whichever comes first. Imaging beyond 5 years is recommended as clinically indicated .
			Nursing Orders
  	ONC NURSING COMMUNICATION 72	Interval: --	Occurrences: --	Comments:	FSKI-19/PROMIS-Fatigue/EQ-5D-5L

For patients registered to A032201-HO1

Year 1 : Every 12w ; Year 2: every 16w, Year 3-5: every 24w
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Blood pressure, body temperature, heart rate
		  	RESEARCH - MEASURE WEIGHT	Interval: --	Occurrences: --			Cardiology
  	ECG 12-LEAD	Interval: --	Occurrences: --			Labs
☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		☑	MAGNESIUM LEVEL	Interval: --	Occurrences: --			Labs
  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	CALCIUM LEVEL	Interval: --	Occurrences: --			Labs
  	THYROID STIMULATING HORMONE	Interval: --	Occurrences: --			Labs
  	CORTISOL LEVEL, AM	Interval: --	Occurrences: --	Comments:	Must be collected in the morning.
			Labs
  	CREATININE CLEARANCE, URINE, 24 HOUR	Interval: --	Occurrences: --			Labs
☐	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
		☐	HCG QUANTITATIVE, SERUM	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
		☑	HCG QUALITATIVE, URINE SCREEN	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
			Labs
◉	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	All patients will have urinalysis or UPCR performed at screening; if urine protein is >=2+, 24-hour urine collection or UPC ratio will be required . If UPCR <2, optimize blood pressure and manage per institutional guidelines .
		◯	URINE PROTEIN/CREATININE RATIO, RANDOM	Interval: --	Occurrences: --	Comments:	All patients will have urinalysis or UPCR performed at screening; if urine protein is >=2+, 24-hour urine collection or UPC ratio will be required . If UPCR <2, optimize blood pressure and manage per institutional guidelines .
			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	C1D1,PTFU, PROGRESSION

PTFU ( 6,12,18,24 months from C1D1)
			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	C1D1,PTFU, PROGRESSION

PTFU ( 6,12,18,24 months from C1D1)
			Chemotherapy
  	ONC NURSING COMMUNICATION 70	Interval: --	Occurrences: --	Comments:	Tivozanib pills will be ordered directly from IDS pharmacy via paper Rx order form
		  	ONC NURSING COMMUNICATION 69	Interval: --	Occurrences: --	Comments:	Tivozanib 1.34 mg once daily on days 1 through 21 of a 28-day cycle.
Take with or without food.
Swallow the tivozanib capsule whole with a glass of water; Do not open the capsule.
Wound healing may be impaired. Administration should be stooped prior to surgery.
Multiple drug-drug or drug-food interactions. Review patient medical profile.
			Oral Chemotherapy
  	ONC NURSING COMMUNICATION 67	Interval: --	Occurrences: --	Comments:	Assess compliance to Tivozanib
		  	ONC NURSING COMMUNICATION 72	Interval: --	Occurrences: --	Comments:	Dose modification and management of Tivozanib treatment: refer to section 8.2.1 of protocol
			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.
			Line Care
  	INSERT PERIPHERAL IV OR ACCESS PORTACATH	Interval: --	Occurrences: --		  	sodium chloride 0.9% flush 20 mL	Dose: 20 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.			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Dose modification and management of Pembrolizumab treatment: refer to section 8.3 of protocol
			Immuno-therapy
  	pembrolizumab (KEYTRUDA) 400 mg in sodium chloride 0.9% 100 mL IVPB	Dose: 400 mg	Route: intravenous	once over 30 Minutes for 1 dose	Start: S			Instructions:	Administer with low protein binding 0.22 micron in-line filter. Do not shake. Do not mix with other medications.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	PEMBROLIZUMAB 25 MG/ML INTRAVENOUS SOLUTION	Medications	400 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	84 mL	Yes	Yes				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.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 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 Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 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.
		  	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 Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) 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.
		  	acetaminophen (TYLENOL) tablet 650 mg	Dose: 650 mg	Route: oral	once PRN	Start: S				  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 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				C2 D29	Perform every 1 day x1			Research tolerance: -0/+0 days	Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Nursing  Communication: Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink:   A032201_Prath
		  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for TIVOZANIB Treatment: Refer to Section 10.2[RA1]   Management of AEs Associated with Refer to section  8.2
Protocol Access Hyperlink:  A032201_Prath
			Nursing Orders
  	ONC NURSING COMMUNICATION 116	Interval: --	Occurrences: --	Comments:	Medical history
			Nursing Orders
  	ONC NURSING COMMUNICATION 75	Interval: --	Occurrences: --	Comments:	Physical Exam

Physical examination and staging scans are required every 16w (+/-2w) for year 1 and 2 after registration; then every 24w (+/-3w)until 5 years from registration or until disease progression, or consent withdrawal, whichever comes first; thereafter, survival information is required every 12 months(+/-2 months) until 10 years from registration.
			Nursing Orders
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Concomitant medications
			Nursing Orders
  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	Adverse Events
			Nursing Orders
  	ONC NURSING COMMUNICATION 71	Interval: --	Occurrences: --	Comments:	Pill compliance must be documented by any member of the care team. If the sample diary in Appendix II or III is used, it should begin the day the patient starts taking medication and should be completed per protocol and returned to the treating institution.
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Blood pressure, body temperature, heart rate
		  	RESEARCH - MEASURE WEIGHT	Interval: --	Occurrences: --			Cardiology
  	ECG 12-LEAD	Interval: --	Occurrences: --			Labs
  	ONC NURSING COMMUNICATION 52	Interval: --	Occurrences: --	Comments:	Labs completed prior to registration may be used for C1D1 test if obtained <= 3 days prior to treatment
			Labs
☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		☑	MAGNESIUM LEVEL	Interval: --	Occurrences: --			Labs
  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	CALCIUM LEVEL	Interval: --	Occurrences: --			Labs
  	THYROID STIMULATING HORMONE	Interval: --	Occurrences: --			Labs
  	CORTISOL LEVEL, AM	Interval: --	Occurrences: --	Comments:	Must be collected in the morning.
			Labs
  	CREATININE CLEARANCE, URINE, 24 HOUR	Interval: --	Occurrences: --			Labs
☐	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
		☐	HCG QUANTITATIVE, SERUM	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
		☑	HCG QUALITATIVE, URINE SCREEN	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
			Labs
◉	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	All patients will have urinalysis or UPCR performed at screening; if urine protein is >=2+, 24-hour urine collection or UPC ratio will be required . If UPCR <2, optimize blood pressure and manage per institutional guidelines .
		◯	URINE PROTEIN/CREATININE RATIO, RANDOM	Interval: --	Occurrences: --	Comments:	All patients will have urinalysis or UPCR performed at screening; if urine protein is >=2+, 24-hour urine collection or UPC ratio will be required . If UPCR <2, optimize blood pressure and manage per institutional guidelines .
			Chemotherapy
  	ONC NURSING COMMUNICATION 70	Interval: --	Occurrences: --	Comments:	Tivozanib pills will be ordered directly from IDS pharmacy via paper Rx order form
		  	ONC NURSING COMMUNICATION 69	Interval: --	Occurrences: --	Comments:	Tivozanib 1.34 mg once daily on days 1 through 21 of a 28-day cycle.
Take with or without food.
Swallow the tivozanib capsule whole with a glass of water; Do not open the capsule.
Wound healing may be impaired. Administration should be stooped prior to surgery.
Multiple drug-drug or drug-food interactions. Review patient medical profile.
			Oral Chemotherapy
  	ONC NURSING COMMUNICATION 67	Interval: --	Occurrences: --	Comments:	Assess compliance to Tivozanib
		  	ONC NURSING COMMUNICATION 72	Interval: --	Occurrences: --	Comments:	Dose modification and management of Tivozanib treatment: refer to section 8.2.1 of protocol
				C2 D43	Perform every 1 day x1			Research tolerance: -0/+0 days	Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Nursing  Communication: Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink:   A032201_Prath
		  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for TIVOZANIB Treatment: Refer to Section 10.2[RA1]   Management of AEs Associated with Refer to section  8.2
Protocol Access Hyperlink:  A032201_Prath
			Nursing Orders
  	ONC NURSING COMMUNICATION 116	Interval: --	Occurrences: --	Comments:	Medical history
			Nursing Orders
  	ONC NURSING COMMUNICATION 75	Interval: --	Occurrences: --	Comments:	Physical Exam

Physical examination and staging scans are required every 16w (+/-2w) for year 1 and 2 after registration; then every 24w (+/-3w)until 5 years from registration or until disease progression, or consent withdrawal, whichever comes first; thereafter, survival information is required every 12 months(+/-2 months) until 10 years from registration.
			Nursing Orders
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Concomitant medications
			Nursing Orders
  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	Adverse Events
			Nursing Orders
  	ONC NURSING COMMUNICATION 71	Interval: --	Occurrences: --	Comments:	Pill compliance must be documented by any member of the care team. If the sample diary in Appendix II or III is used, it should begin the day the patient starts taking medication and should be completed per protocol and returned to the treating institution.
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Blood pressure, body temperature, heart rate
		  	RESEARCH - MEASURE WEIGHT	Interval: --	Occurrences: --			Cardiology
  	ECG 12-LEAD	Interval: --	Occurrences: --			Labs
  	ONC NURSING COMMUNICATION 52	Interval: --	Occurrences: --	Comments:	Labs completed prior to registration may be used for C1D1 test if obtained <= 3 days prior to treatment
			Labs
☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		☑	MAGNESIUM LEVEL	Interval: --	Occurrences: --			Labs
  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	CALCIUM LEVEL	Interval: --	Occurrences: --			Labs
  	THYROID STIMULATING HORMONE	Interval: --	Occurrences: --			Labs
  	CORTISOL LEVEL, AM	Interval: --	Occurrences: --	Comments:	Must be collected in the morning.
			Labs
  	CREATININE CLEARANCE, URINE, 24 HOUR	Interval: --	Occurrences: --			Labs
☐	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
		☐	HCG QUANTITATIVE, SERUM	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
		☑	HCG QUALITATIVE, URINE SCREEN	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
			Labs
◉	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	All patients will have urinalysis or UPCR performed at screening; if urine protein is >=2+, 24-hour urine collection or UPC ratio will be required . If UPCR <2, optimize blood pressure and manage per institutional guidelines .
		◯	URINE PROTEIN/CREATININE RATIO, RANDOM	Interval: --	Occurrences: --	Comments:	All patients will have urinalysis or UPCR performed at screening; if urine protein is >=2+, 24-hour urine collection or UPC ratio will be required . If UPCR <2, optimize blood pressure and manage per institutional guidelines .
			Chemotherapy
  	ONC NURSING COMMUNICATION 70	Interval: --	Occurrences: --	Comments:	Tivozanib pills will be ordered directly from IDS pharmacy via paper Rx order form
		  	ONC NURSING COMMUNICATION 69	Interval: --	Occurrences: --	Comments:	Tivozanib 1.34 mg once daily on days 1 through 21 of a 28-day cycle.
Take with or without food.
Swallow the tivozanib capsule whole with a glass of water; Do not open the capsule.
Wound healing may be impaired. Administration should be stooped prior to surgery.
Multiple drug-drug or drug-food interactions. Review patient medical profile.
			Oral Chemotherapy
  	ONC NURSING COMMUNICATION 67	Interval: --	Occurrences: --	Comments:	Assess compliance to Tivozanib
		  	ONC NURSING COMMUNICATION 72	Interval: --	Occurrences: --	Comments:	Dose modification and management of Tivozanib treatment: refer to section 8.2.1 of protocol
			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.
			Line Care
  	INSERT PERIPHERAL IV OR ACCESS PORTACATH	Interval: --	Occurrences: --		  	sodium chloride 0.9% flush 20 mL	Dose: 20 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.			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Dose modification and management of Pembrolizumab treatment: refer to section 8.3 of protocol
			Immuno-therapy
  	pembrolizumab (KEYTRUDA) 400 mg in sodium chloride 0.9% 100 mL IVPB	Dose: 400 mg	Route: intravenous	once over 30 Minutes for 1 dose	Start: S			Instructions:	Administer with low protein binding 0.22 micron in-line filter. Do not shake. Do not mix with other medications.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	PEMBROLIZUMAB 25 MG/ML INTRAVENOUS SOLUTION	Medications	400 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	84 mL	Yes	Yes				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.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 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 Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 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.
		  	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 Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) 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.
		  	acetaminophen (TYLENOL) tablet 650 mg	Dose: 650 mg	Route: oral	once PRN	Start: S				  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 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				C2 D57	Perform every 1 day x1			Research tolerance: -0/+0 days	Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Nursing  Communication: Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink:   A032201_Prath
		  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for TIVOZANIB Treatment: Refer to Section 10.2[RA1]   Management of AEs Associated with Refer to section  8.2
Protocol Access Hyperlink:  A032201_Prath
			Nursing Orders
  	ONC NURSING COMMUNICATION 116	Interval: --	Occurrences: --	Comments:	Medical history
			Nursing Orders
  	ONC NURSING COMMUNICATION 75	Interval: --	Occurrences: --	Comments:	Physical Exam

Physical examination and staging scans are required every 16w (+/-2w) for year 1 and 2 after registration; then every 24w (+/-3w)until 5 years from registration or until disease progression, or consent withdrawal, whichever comes first; thereafter, survival information is required every 12 months(+/-2 months) until 10 years from registration.
			Nursing Orders
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Concomitant medications
			Nursing Orders
  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	Adverse Events
			Nursing Orders
  	ONC NURSING COMMUNICATION 71	Interval: --	Occurrences: --	Comments:	Pill compliance must be documented by any member of the care team. If the sample diary in Appendix II or III is used, it should begin the day the patient starts taking medication and should be completed per protocol and returned to the treating institution.
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Blood pressure, body temperature, heart rate
		  	RESEARCH - MEASURE WEIGHT	Interval: --	Occurrences: --			Cardiology
  	ECG 12-LEAD	Interval: --	Occurrences: --			Labs
☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		☑	MAGNESIUM LEVEL	Interval: --	Occurrences: --			Labs
  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	CALCIUM LEVEL	Interval: --	Occurrences: --			Labs
  	THYROID STIMULATING HORMONE	Interval: --	Occurrences: --			Labs
  	CORTISOL LEVEL, AM	Interval: --	Occurrences: --	Comments:	Must be collected in the morning.
			Labs
  	CREATININE CLEARANCE, URINE, 24 HOUR	Interval: --	Occurrences: --			Labs
☐	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
		☐	HCG QUANTITATIVE, SERUM	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
		☑	HCG QUALITATIVE, URINE SCREEN	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
			Labs
◉	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	All patients will have urinalysis or UPCR performed at screening; if urine protein is >=2+, 24-hour urine collection or UPC ratio will be required . If UPCR <2, optimize blood pressure and manage per institutional guidelines .
		◯	URINE PROTEIN/CREATININE RATIO, RANDOM	Interval: --	Occurrences: --	Comments:	All patients will have urinalysis or UPCR performed at screening; if urine protein is >=2+, 24-hour urine collection or UPC ratio will be required . If UPCR <2, optimize blood pressure and manage per institutional guidelines .
			Chemotherapy
  	ONC NURSING COMMUNICATION 70	Interval: --	Occurrences: --	Comments:	Tivozanib pills will be ordered directly from IDS pharmacy via paper Rx order form
		  	ONC NURSING COMMUNICATION 69	Interval: --	Occurrences: --	Comments:	Tivozanib 1.34 mg once daily on days 1 through 21 of a 28-day cycle.
Take with or without food.
Swallow the tivozanib capsule whole with a glass of water; Do not open the capsule.
Wound healing may be impaired. Administration should be stooped prior to surgery.
Multiple drug-drug or drug-food interactions. Review patient medical profile.
			Oral Chemotherapy
  	ONC NURSING COMMUNICATION 67	Interval: --	Occurrences: --	Comments:	Assess compliance to Tivozanib
		  	ONC NURSING COMMUNICATION 72	Interval: --	Occurrences: --	Comments:	Dose modification and management of Tivozanib treatment: refer to section 8.2.1 of protocol
					
Cycle 3	Repeat 1 time	Cycle length: 84 days	C3 D1	Perform every 1 day x1			Research tolerance: -0/+0 days	Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Nursing  Communication: Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink:   A032201_Prath
		  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for TIVOZANIB Treatment: Refer to Section 10.2[RA1]   Management of AEs Associated with Refer to section  8.2
Protocol Access Hyperlink:  A032201_Prath
			Nursing Orders
  	ONC NURSING COMMUNICATION 116	Interval: --	Occurrences: --	Comments:	Medical history
			Nursing Orders
  	ONC NURSING COMMUNICATION 75	Interval: --	Occurrences: --	Comments:	Physical Exam

Physical examination and staging scans are required every 16w (+/-2w) for year 1 and 2 after registration; then every 24w (+/-3w)until 5 years from registration or until disease progression, or consent withdrawal, whichever comes first; thereafter, survival information is required every 12 months(+/-2 months) until 10 years from registration.
			Nursing Orders
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Concomitant medications
			Nursing Orders
  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	Adverse Events
			Nursing Orders
  	ONC NURSING COMMUNICATION 71	Interval: --	Occurrences: --	Comments:	Pill compliance must be documented by any member of the care team. If the sample diary in Appendix II or III is used, it should begin the day the patient starts taking medication and should be completed per protocol and returned to the treating institution.
			Imaging
◯	CT HEAD W CONTRAST	Interval: --	Occurrences: --	Comments:	MRI or CT
		◯	CT HEAD W WO CONTRAST	Interval: --	Occurrences: --	Comments:	MRI or CT
		◯	CT HEAD WO CONTRAST	Interval: --	Occurrences: --	Comments:	MRI or CT
		◉	MRI BRAIN W WO CONTRAST	Interval: --	Occurrences: --	Comments:	MRI or CT
		◯	MRI BRAIN W CONTRAST	Interval: --	Occurrences: --	Comments:	MRI or CT
		◯	MRI BRAIN WO CONTRAST	Interval: --	Occurrences: --	Comments:	MRI or CT
			Imaging
☑	CT CHEST W WO CONTRAST ABDOMEN W CONTRAST PELVIS W CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI 

CT pelvis is as clinically indicated . Imaging scans (with or without contrast) will be obtained prior to registration and then every 12 weeks +/- 2 weeks during the first year, and then every 16 weeks, +/- 3 weeks for second year, every 24 weeks +/- 3 weeks for 3 years , then annually +/-4 weeks until 5 years after registration or progression , whichever comes first. Imaging beyond 5 years is recommended as clinically indicated .
		☐	MRI CHEST W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI 

CT pelvis is as clinically indicated . Imaging scans (with or without contrast) will be obtained prior to registration and then every 12 weeks +/- 2 weeks during the first year, and then every 16 weeks, +/- 3 weeks for second year, every 24 weeks +/- 3 weeks for 3 years , then annually +/-4 weeks until 5 years after registration or progression , whichever comes first. Imaging beyond 5 years is recommended as clinically indicated .
		☐	MRI ABDOMEN W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI

CT pelvis is as clinically indicated . Imaging scans (with or without contrast) will be obtained prior to registration and then every 12 weeks +/- 2 weeks during the first year, and then every 16 weeks, +/- 3 weeks for second year, every 24 weeks +/- 3 weeks for 3 years , then annually +/-4 weeks until 5 years after registration or progression , whichever comes first. Imaging beyond 5 years is recommended as clinically indicated .
		☐	MRI PELVIS W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI 

CT pelvis is as clinically indicated . Imaging scans (with or without contrast) will be obtained prior to registration and then every 12 weeks +/- 2 weeks during the first year, and then every 16 weeks, +/- 3 weeks for second year, every 24 weeks +/- 3 weeks for 3 years , then annually +/-4 weeks until 5 years after registration or progression , whichever comes first. Imaging beyond 5 years is recommended as clinically indicated .
			Nursing Orders
  	ONC NURSING COMMUNICATION 72	Interval: --	Occurrences: --	Comments:	FSKI-19/PROMIS-Fatigue/EQ-5D-5L

For patients registered to A032201-HO1

Year 1 : Every 12w ; Year 2: every 16w, Year 3-5: every 24w
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Blood pressure, body temperature, heart rate
		  	RESEARCH - MEASURE WEIGHT	Interval: --	Occurrences: --			Cardiology
  	ECG 12-LEAD	Interval: --	Occurrences: --			Labs
☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		☑	MAGNESIUM LEVEL	Interval: --	Occurrences: --			Labs
  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	CALCIUM LEVEL	Interval: --	Occurrences: --			Labs
  	THYROID STIMULATING HORMONE	Interval: --	Occurrences: --			Labs
  	CORTISOL LEVEL, AM	Interval: --	Occurrences: --	Comments:	Must be collected in the morning.
			Labs
  	CREATININE CLEARANCE, URINE, 24 HOUR	Interval: --	Occurrences: --			Labs
☐	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
		☐	HCG QUANTITATIVE, SERUM	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
		☑	HCG QUALITATIVE, URINE SCREEN	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
			Labs
◉	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	All patients will have urinalysis or UPCR performed at screening; if urine protein is >=2+, 24-hour urine collection or UPC ratio will be required . If UPCR <2, optimize blood pressure and manage per institutional guidelines .
		◯	URINE PROTEIN/CREATININE RATIO, RANDOM	Interval: --	Occurrences: --	Comments:	All patients will have urinalysis or UPCR performed at screening; if urine protein is >=2+, 24-hour urine collection or UPC ratio will be required . If UPCR <2, optimize blood pressure and manage per institutional guidelines .
			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	C1D1,PTFU, PROGRESSION

PTFU ( 6,12,18,24 months from C1D1)
			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	C1D1,PTFU, PROGRESSION

PTFU ( 6,12,18,24 months from C1D1)
			Chemotherapy
  	ONC NURSING COMMUNICATION 70	Interval: --	Occurrences: --	Comments:	Tivozanib pills will be ordered directly from IDS pharmacy via paper Rx order form
		  	ONC NURSING COMMUNICATION 69	Interval: --	Occurrences: --	Comments:	Tivozanib 1.34 mg once daily on days 1 through 21 of a 28-day cycle.
Take with or without food.
Swallow the tivozanib capsule whole with a glass of water; Do not open the capsule.
Wound healing may be impaired. Administration should be stooped prior to surgery.
Multiple drug-drug or drug-food interactions. Review patient medical profile.
			Oral Chemotherapy
  	ONC NURSING COMMUNICATION 67	Interval: --	Occurrences: --	Comments:	Assess compliance to Tivozanib
		  	ONC NURSING COMMUNICATION 72	Interval: --	Occurrences: --	Comments:	Dose modification and management of Tivozanib treatment: refer to section 8.2.1 of protocol
			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.
			Line Care
  	INSERT PERIPHERAL IV OR ACCESS PORTACATH	Interval: --	Occurrences: --		  	sodium chloride 0.9% flush 20 mL	Dose: 20 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.			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Dose modification and management of Pembrolizumab treatment: refer to section 8.3 of protocol
			Immuno-therapy
  	pembrolizumab (KEYTRUDA) 400 mg in sodium chloride 0.9% 100 mL IVPB	Dose: 400 mg	Route: intravenous	once over 30 Minutes for 1 dose	Start: S			Instructions:	Administer with low protein binding 0.22 micron in-line filter. Do not shake. Do not mix with other medications.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	PEMBROLIZUMAB 25 MG/ML INTRAVENOUS SOLUTION	Medications	400 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	84 mL	Yes	Yes				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.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 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 Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 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.
		  	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 Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) 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.
		  	acetaminophen (TYLENOL) tablet 650 mg	Dose: 650 mg	Route: oral	once PRN	Start: S				  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 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				C3 D43	Perform every 1 day x1			Research tolerance: -0/+0 days	Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Nursing  Communication: Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink:   A032201_Prath
		  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for TIVOZANIB Treatment: Refer to Section 10.2[RA1]   Management of AEs Associated with Refer to section  8.2
Protocol Access Hyperlink:  A032201_Prath
			Nursing Orders
  	ONC NURSING COMMUNICATION 116	Interval: --	Occurrences: --	Comments:	Medical history
			Nursing Orders
  	ONC NURSING COMMUNICATION 75	Interval: --	Occurrences: --	Comments:	Physical Exam

Physical examination and staging scans are required every 16w (+/-2w) for year 1 and 2 after registration; then every 24w (+/-3w)until 5 years from registration or until disease progression, or consent withdrawal, whichever comes first; thereafter, survival information is required every 12 months(+/-2 months) until 10 years from registration.
			Nursing Orders
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Concomitant medications
			Nursing Orders
  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	Adverse Events
			Nursing Orders
  	ONC NURSING COMMUNICATION 71	Interval: --	Occurrences: --	Comments:	Pill compliance must be documented by any member of the care team. If the sample diary in Appendix II or III is used, it should begin the day the patient starts taking medication and should be completed per protocol and returned to the treating institution.
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Blood pressure, body temperature, heart rate
		  	RESEARCH - MEASURE WEIGHT	Interval: --	Occurrences: --			Cardiology
  	ECG 12-LEAD	Interval: --	Occurrences: --			Labs
  	ONC NURSING COMMUNICATION 52	Interval: --	Occurrences: --	Comments:	Labs completed prior to registration may be used for C1D1 test if obtained <= 3 days prior to treatment
			Labs
☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		☑	MAGNESIUM LEVEL	Interval: --	Occurrences: --			Labs
  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	CALCIUM LEVEL	Interval: --	Occurrences: --			Labs
  	THYROID STIMULATING HORMONE	Interval: --	Occurrences: --			Labs
  	CORTISOL LEVEL, AM	Interval: --	Occurrences: --	Comments:	Must be collected in the morning.
			Labs
  	CREATININE CLEARANCE, URINE, 24 HOUR	Interval: --	Occurrences: --			Labs
☐	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
		☐	HCG QUANTITATIVE, SERUM	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
		☑	HCG QUALITATIVE, URINE SCREEN	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
			Labs
◉	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	All patients will have urinalysis or UPCR performed at screening; if urine protein is >=2+, 24-hour urine collection or UPC ratio will be required . If UPCR <2, optimize blood pressure and manage per institutional guidelines .
		◯	URINE PROTEIN/CREATININE RATIO, RANDOM	Interval: --	Occurrences: --	Comments:	All patients will have urinalysis or UPCR performed at screening; if urine protein is >=2+, 24-hour urine collection or UPC ratio will be required . If UPCR <2, optimize blood pressure and manage per institutional guidelines .
			Chemotherapy
  	ONC NURSING COMMUNICATION 70	Interval: --	Occurrences: --	Comments:	Tivozanib pills will be ordered directly from IDS pharmacy via paper Rx order form
		  	ONC NURSING COMMUNICATION 69	Interval: --	Occurrences: --	Comments:	Tivozanib 1.34 mg once daily on days 1 through 21 of a 28-day cycle.
Take with or without food.
Swallow the tivozanib capsule whole with a glass of water; Do not open the capsule.
Wound healing may be impaired. Administration should be stooped prior to surgery.
Multiple drug-drug or drug-food interactions. Review patient medical profile.
			Oral Chemotherapy
  	ONC NURSING COMMUNICATION 67	Interval: --	Occurrences: --	Comments:	Assess compliance to Tivozanib
		  	ONC NURSING COMMUNICATION 72	Interval: --	Occurrences: --	Comments:	Dose modification and management of Tivozanib treatment: refer to section 8.2.1 of protocol
			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.
			Line Care
  	INSERT PERIPHERAL IV OR ACCESS PORTACATH	Interval: --	Occurrences: --		  	sodium chloride 0.9% flush 20 mL	Dose: 20 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.			Immuno-therapy
  	pembrolizumab (KEYTRUDA) 400 mg in sodium chloride 0.9% 100 mL IVPB	Dose: 400 mg	Route: intravenous	once over 30 Minutes for 1 dose	Start: S			Instructions:	Administer with low protein binding 0.22 micron in-line filter. Do not shake. Do not mix with other medications.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	PEMBROLIZUMAB 25 MG/ML INTRAVENOUS SOLUTION	Medications	400 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	84 mL	Yes	Yes				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.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 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 Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 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.
		  	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 Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) 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.
		  	acetaminophen (TYLENOL) tablet 650 mg	Dose: 650 mg	Route: oral	once PRN	Start: S				  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 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 4	Repeat 1 time	Cycle length: 84 days	C4 D1	Perform every 1 day x1			Research tolerance: -0/+0 days	Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Nursing  Communication: Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink:   A032201_Prath
		  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for TIVOZANIB Treatment: Refer to Section 10.2[RA1]   Management of AEs Associated with Refer to section  8.2
Protocol Access Hyperlink:  A032201_Prath
			Nursing Orders
  	ONC NURSING COMMUNICATION 116	Interval: --	Occurrences: --	Comments:	Medical history
			Nursing Orders
  	ONC NURSING COMMUNICATION 75	Interval: --	Occurrences: --	Comments:	Physical Exam

Physical examination and staging scans are required every 16w (+/-2w) for year 1 and 2 after registration; then every 24w (+/-3w)until 5 years from registration or until disease progression, or consent withdrawal, whichever comes first; thereafter, survival information is required every 12 months(+/-2 months) until 10 years from registration.
			Nursing Orders
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Concomitant medications
			Nursing Orders
  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	Adverse Events
			Nursing Orders
  	ONC NURSING COMMUNICATION 71	Interval: --	Occurrences: --	Comments:	Pill compliance must be documented by any member of the care team. If the sample diary in Appendix II or III is used, it should begin the day the patient starts taking medication and should be completed per protocol and returned to the treating institution.
			Imaging
◯	CT HEAD W CONTRAST	Interval: --	Occurrences: --	Comments:	MRI or CT
		◯	CT HEAD W WO CONTRAST	Interval: --	Occurrences: --	Comments:	MRI or CT
		◯	CT HEAD WO CONTRAST	Interval: --	Occurrences: --	Comments:	MRI or CT
		◉	MRI BRAIN W WO CONTRAST	Interval: --	Occurrences: --	Comments:	MRI or CT
		◯	MRI BRAIN W CONTRAST	Interval: --	Occurrences: --	Comments:	MRI or CT
		◯	MRI BRAIN WO CONTRAST	Interval: --	Occurrences: --	Comments:	MRI or CT
			Imaging
☑	CT CHEST W WO CONTRAST ABDOMEN W CONTRAST PELVIS W CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI 

CT pelvis is as clinically indicated . Imaging scans (with or without contrast) will be obtained prior to registration and then every 12 weeks +/- 2 weeks during the first year, and then every 16 weeks, +/- 3 weeks for second year, every 24 weeks +/- 3 weeks for 3 years , then annually +/-4 weeks until 5 years after registration or progression , whichever comes first. Imaging beyond 5 years is recommended as clinically indicated .
		☐	MRI CHEST W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI 

CT pelvis is as clinically indicated . Imaging scans (with or without contrast) will be obtained prior to registration and then every 12 weeks +/- 2 weeks during the first year, and then every 16 weeks, +/- 3 weeks for second year, every 24 weeks +/- 3 weeks for 3 years , then annually +/-4 weeks until 5 years after registration or progression , whichever comes first. Imaging beyond 5 years is recommended as clinically indicated .
		☐	MRI ABDOMEN W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI

CT pelvis is as clinically indicated . Imaging scans (with or without contrast) will be obtained prior to registration and then every 12 weeks +/- 2 weeks during the first year, and then every 16 weeks, +/- 3 weeks for second year, every 24 weeks +/- 3 weeks for 3 years , then annually +/-4 weeks until 5 years after registration or progression , whichever comes first. Imaging beyond 5 years is recommended as clinically indicated .
		☐	MRI PELVIS W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI 

CT pelvis is as clinically indicated . Imaging scans (with or without contrast) will be obtained prior to registration and then every 12 weeks +/- 2 weeks during the first year, and then every 16 weeks, +/- 3 weeks for second year, every 24 weeks +/- 3 weeks for 3 years , then annually +/-4 weeks until 5 years after registration or progression , whichever comes first. Imaging beyond 5 years is recommended as clinically indicated .
			Nursing Orders
  	ONC NURSING COMMUNICATION 72	Interval: --	Occurrences: --	Comments:	FSKI-19/PROMIS-Fatigue/EQ-5D-5L

For patients registered to A032201-HO1

Year 1 : Every 12w ; Year 2: every 16w, Year 3-5: every 24w
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Blood pressure, body temperature, heart rate
		  	RESEARCH - MEASURE WEIGHT	Interval: --	Occurrences: --			Cardiology
  	ECG 12-LEAD	Interval: --	Occurrences: --			Labs
☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		☑	MAGNESIUM LEVEL	Interval: --	Occurrences: --			Labs
  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	CALCIUM LEVEL	Interval: --	Occurrences: --			Labs
  	THYROID STIMULATING HORMONE	Interval: --	Occurrences: --			Labs
  	CORTISOL LEVEL, AM	Interval: --	Occurrences: --	Comments:	Must be collected in the morning.
			Labs
  	CREATININE CLEARANCE, URINE, 24 HOUR	Interval: --	Occurrences: --			Labs
☐	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
		☐	HCG QUANTITATIVE, SERUM	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
		☑	HCG QUALITATIVE, URINE SCREEN	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
			Labs
◉	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	All patients will have urinalysis or UPCR performed at screening; if urine protein is >=2+, 24-hour urine collection or UPC ratio will be required . If UPCR <2, optimize blood pressure and manage per institutional guidelines .
		◯	URINE PROTEIN/CREATININE RATIO, RANDOM	Interval: --	Occurrences: --	Comments:	All patients will have urinalysis or UPCR performed at screening; if urine protein is >=2+, 24-hour urine collection or UPC ratio will be required . If UPCR <2, optimize blood pressure and manage per institutional guidelines .
			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	C1D1,PTFU, PROGRESSION

PTFU ( 6,12,18,24 months from C1D1)
			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	C1D1,PTFU, PROGRESSION

PTFU ( 6,12,18,24 months from C1D1)
			Chemotherapy
  	ONC NURSING COMMUNICATION 70	Interval: --	Occurrences: --	Comments:	Tivozanib pills will be ordered directly from IDS pharmacy via paper Rx order form
		  	ONC NURSING COMMUNICATION 69	Interval: --	Occurrences: --	Comments:	Tivozanib 1.34 mg once daily on days 1 through 21 of a 28-day cycle.
Take with or without food.
Swallow the tivozanib capsule whole with a glass of water; Do not open the capsule.
Wound healing may be impaired. Administration should be stooped prior to surgery.
Multiple drug-drug or drug-food interactions. Review patient medical profile.
			Oral Chemotherapy
  	ONC NURSING COMMUNICATION 67	Interval: --	Occurrences: --	Comments:	Assess compliance to Tivozanib
		  	ONC NURSING COMMUNICATION 72	Interval: --	Occurrences: --	Comments:	Dose modification and management of Tivozanib treatment: refer to section 8.2.1 of protocol
			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.
			Line Care
  	INSERT PERIPHERAL IV OR ACCESS PORTACATH	Interval: --	Occurrences: --		  	sodium chloride 0.9% flush 20 mL	Dose: 20 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.			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Dose modification and management of Pembrolizumab treatment: refer to section 8.3 of protocol
			Immuno-therapy
  	pembrolizumab (KEYTRUDA) 400 mg in sodium chloride 0.9% 100 mL IVPB	Dose: 400 mg	Route: intravenous	once over 30 Minutes for 1 dose	Start: S			Instructions:	Administer with low protein binding 0.22 micron in-line filter. Do not shake. Do not mix with other medications.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	PEMBROLIZUMAB 25 MG/ML INTRAVENOUS SOLUTION	Medications	400 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	84 mL	Yes	Yes				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.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 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 Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 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.
		  	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 Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) 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.
		  	acetaminophen (TYLENOL) tablet 650 mg	Dose: 650 mg	Route: oral	once PRN	Start: S				  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 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				C4 D43	Perform every 1 day x1			Research tolerance: -0/+0 days	Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Nursing  Communication: Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink:   A032201_Prath
		  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for TIVOZANIB Treatment: Refer to Section 10.2[RA1]   Management of AEs Associated with Refer to section  8.2
Protocol Access Hyperlink:  A032201_Prath
			Nursing Orders
  	ONC NURSING COMMUNICATION 116	Interval: --	Occurrences: --	Comments:	Medical history
			Nursing Orders
  	ONC NURSING COMMUNICATION 75	Interval: --	Occurrences: --	Comments:	Physical Exam

Physical examination and staging scans are required every 16w (+/-2w) for year 1 and 2 after registration; then every 24w (+/-3w)until 5 years from registration or until disease progression, or consent withdrawal, whichever comes first; thereafter, survival information is required every 12 months(+/-2 months) until 10 years from registration.
			Nursing Orders
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Concomitant medications
			Nursing Orders
  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	Adverse Events
			Nursing Orders
  	ONC NURSING COMMUNICATION 71	Interval: --	Occurrences: --	Comments:	Pill compliance must be documented by any member of the care team. If the sample diary in Appendix II or III is used, it should begin the day the patient starts taking medication and should be completed per protocol and returned to the treating institution.
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Blood pressure, body temperature, heart rate
		  	RESEARCH - MEASURE WEIGHT	Interval: --	Occurrences: --			Cardiology
  	ECG 12-LEAD	Interval: --	Occurrences: --			Labs
  	ONC NURSING COMMUNICATION 52	Interval: --	Occurrences: --	Comments:	Labs completed prior to registration may be used for C1D1 test if obtained <= 3 days prior to treatment
			Labs
☑	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		☑	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		☑	MAGNESIUM LEVEL	Interval: --	Occurrences: --			Labs
  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	CALCIUM LEVEL	Interval: --	Occurrences: --			Labs
  	THYROID STIMULATING HORMONE	Interval: --	Occurrences: --			Labs
  	CORTISOL LEVEL, AM	Interval: --	Occurrences: --	Comments:	Must be collected in the morning.
			Labs
  	CREATININE CLEARANCE, URINE, 24 HOUR	Interval: --	Occurrences: --			Labs
☐	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
		☐	HCG QUANTITATIVE, SERUM	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
		☑	HCG QUALITATIVE, URINE SCREEN	Interval: --	Occurrences: --	Comments:	Serum or Urine HCG. For women of childbearing potential only. At baseline , testing must include a highly sensitive serum beta HCG test. All other visits , serum or urine HCG can be used . WOCB require a negative pregnancy test within either 24 hours (urine ) or 72 hours (serum) before dispensing or infusing study drug .
			Labs
◉	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	All patients will have urinalysis or UPCR performed at screening; if urine protein is >=2+, 24-hour urine collection or UPC ratio will be required . If UPCR <2, optimize blood pressure and manage per institutional guidelines .
		◯	URINE PROTEIN/CREATININE RATIO, RANDOM	Interval: --	Occurrences: --	Comments:	All patients will have urinalysis or UPCR performed at screening; if urine protein is >=2+, 24-hour urine collection or UPC ratio will be required . If UPCR <2, optimize blood pressure and manage per institutional guidelines .
			Chemotherapy
  	ONC NURSING COMMUNICATION 70	Interval: --	Occurrences: --	Comments:	Tivozanib pills will be ordered directly from IDS pharmacy via paper Rx order form
		  	ONC NURSING COMMUNICATION 69	Interval: --	Occurrences: --	Comments:	Tivozanib 1.34 mg once daily on days 1 through 21 of a 28-day cycle.
Take with or without food.
Swallow the tivozanib capsule whole with a glass of water; Do not open the capsule.
Wound healing may be impaired. Administration should be stooped prior to surgery.
Multiple drug-drug or drug-food interactions. Review patient medical profile.
			Oral Chemotherapy
  	ONC NURSING COMMUNICATION 67	Interval: --	Occurrences: --	Comments:	Assess compliance to Tivozanib
		  	ONC NURSING COMMUNICATION 72	Interval: --	Occurrences: --	Comments:	Dose modification and management of Tivozanib treatment: refer to section 8.2.1 of protocol
			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.
			Line Care
  	INSERT PERIPHERAL IV OR ACCESS PORTACATH	Interval: --	Occurrences: --		  	sodium chloride 0.9% flush 20 mL	Dose: 20 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.			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Dose modification and management of Pembrolizumab treatment: refer to section 8.3 of protocol
			Immuno-therapy
  	pembrolizumab (KEYTRUDA) 400 mg in sodium chloride 0.9% 100 mL IVPB	Dose: 400 mg	Route: intravenous	once over 30 Minutes for 1 dose	Start: S			Instructions:	Administer with low protein binding 0.22 micron in-line filter. Do not shake. Do not mix with other medications.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	PEMBROLIZUMAB 25 MG/ML INTRAVENOUS SOLUTION	Medications	400 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	84 mL	Yes	Yes				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.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 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 Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 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.
		  	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 Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) 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.
		  	acetaminophen (TYLENOL) tablet 650 mg	Dose: 650 mg	Route: oral	once PRN	Start: S				  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 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					
PTFU	Repeat 1 time	Cycle length: 1 day	C1 D1	Perform every 1 day x1			Research tolerance: -0/+0 days	Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Nursing  Communication: Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink:   A032201_Prath
		  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for TIVOZANIB Treatment: Refer to Section 10.2[RA1]   Management of AEs Associated with Refer to section  8.2
Protocol Access Hyperlink:  A032201_Prath
			Nursing Orders
  	ONC NURSING COMMUNICATION 116	Interval: --	Occurrences: --	Comments:	Medical history
			Nursing Orders
  	ONC NURSING COMMUNICATION 75	Interval: --	Occurrences: --	Comments:	Physical Exam

Physical examination and staging scans are required every 16w (+/-2w) for year 1 and 2 after registration; then every 24w (+/-3w)until 5 years from registration or until disease progression, or consent withdrawal, whichever comes first; thereafter, survival information is required every 12 months(+/-2 months) until 10 years from registration.
			Nursing Orders
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Concomitant medications
			Imaging
◯	CT HEAD W CONTRAST	Interval: --	Occurrences: --	Comments:	MRI or CT
		◯	CT HEAD W WO CONTRAST	Interval: --	Occurrences: --	Comments:	MRI or CT
		◯	CT HEAD WO CONTRAST	Interval: --	Occurrences: --	Comments:	MRI or CT
		◉	MRI BRAIN W WO CONTRAST	Interval: --	Occurrences: --	Comments:	MRI or CT
		◯	MRI BRAIN W CONTRAST	Interval: --	Occurrences: --	Comments:	MRI or CT
		◯	MRI BRAIN WO CONTRAST	Interval: --	Occurrences: --	Comments:	MRI or CT
			Imaging
☑	CT CHEST W WO CONTRAST ABDOMEN W CONTRAST PELVIS W CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI 

CT pelvis is as clinically indicated . Imaging scans (with or without contrast) will be obtained prior to registration and then every 12 weeks +/- 2 weeks during the first year, and then every 16 weeks, +/- 3 weeks for second year, every 24 weeks +/- 3 weeks for 3 years , then annually +/-4 weeks until 5 years after registration or progression , whichever comes first. Imaging beyond 5 years is recommended as clinically indicated .
		☐	MRI CHEST W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI 

CT pelvis is as clinically indicated . Imaging scans (with or without contrast) will be obtained prior to registration and then every 12 weeks +/- 2 weeks during the first year, and then every 16 weeks, +/- 3 weeks for second year, every 24 weeks +/- 3 weeks for 3 years , then annually +/-4 weeks until 5 years after registration or progression , whichever comes first. Imaging beyond 5 years is recommended as clinically indicated .
		☐	MRI ABDOMEN W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI

CT pelvis is as clinically indicated . Imaging scans (with or without contrast) will be obtained prior to registration and then every 12 weeks +/- 2 weeks during the first year, and then every 16 weeks, +/- 3 weeks for second year, every 24 weeks +/- 3 weeks for 3 years , then annually +/-4 weeks until 5 years after registration or progression , whichever comes first. Imaging beyond 5 years is recommended as clinically indicated .
		☐	MRI PELVIS W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI 

CT pelvis is as clinically indicated . Imaging scans (with or without contrast) will be obtained prior to registration and then every 12 weeks +/- 2 weeks during the first year, and then every 16 weeks, +/- 3 weeks for second year, every 24 weeks +/- 3 weeks for 3 years , then annually +/-4 weeks until 5 years after registration or progression , whichever comes first. Imaging beyond 5 years is recommended as clinically indicated .
			Nursing Orders
  	ONC NURSING COMMUNICATION 72	Interval: --	Occurrences: --	Comments:	FSKI-19/PROMIS-Fatigue/EQ-5D-5L

For patients registered to A032201-HO1

Year 1 : Every 12w ; Year 2: every 16w, Year 3-5: every 24w
			Cardiology
  	ECG 12-LEAD	Interval: --	Occurrences: --			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --			Labs
  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	CALCIUM LEVEL	Interval: --	Occurrences: --			Labs
  	CREATININE CLEARANCE, URINE, 24 HOUR	Interval: --	Occurrences: --			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	C1D1,PTFU, PROGRESSION

PTFU ( 6,12,18,24 months from C1D1)
			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	C1D1,PTFU, PROGRESSION

PTFU ( 6,12,18,24 months from C1D1)
					
Progression	Repeat 1 time	Cycle length: 1 day	Day 1	Perform every 1 day x1			Research tolerance: -0/+0 days	Nursing Orders
  	ONC NURSING COMMUNICATION 72	Interval: --	Occurrences: --	Comments:	FSKI-19/PROMIS-Fatigue/EQ-5D-5L

For patients registered to A032201-HO1

Year 1 : Every 12w ; Year 2: every 16w, Year 3-5: every 24w
			Nursing Orders
  	ONC NURSING COMMUNICATION 72	Interval: --	Occurrences: --	Comments:	Progression samples may be collected and submitted up to 60 days after progression but before the initiation of subsequent therapy
			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	C1D1,PTFU, PROGRESSION

PTFU ( 6,12,18,24 months from C1D1)
			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	C1D1,PTFU, PROGRESSION

PTFU ( 6,12,18,24 months from C1D1)