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OP PRO00038124 / ARM 2 (OP AC + PEMBROLIZUMAB) – NEOADJUVANT SETTING (CONTROL)	

Types:      Research Oncology Treatment
Synonyms:  BREAST CANCER, D926QC00001, CONTROL ARM, NEOADJUVANT

Cycle 1	Repeat 1 time	Cycle length: 21 days	Day 1	Perform every 1 day x1			Research tolerance: -3/+3 days	Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Inclusion/exclusion criteria.

If screening assessments have been performed within 3 days prior to starting study intervention, they do not have to be repeated at C1 Day 1 if the participant's condition has not changed
		  	ONC NURSING COMMUNCATION 101	Interval: --	Occurrences: --	Comments:	Randomization.

Every effort should be made to minimise the time between randomisation and starting treatment (ie, within 3 business days of randomisation).
		  	ONC NURSING COMMUNCATION 101	Interval: --	Occurrences: --	Comments:	Medical History and current medical conditions.

If screening assessments have been performed within 3 days prior to starting study intervention, they do not have to be repeated at C1 Day 1 if the participant's condition has not changed
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Full physical examination 

If screening assessments have been performed within 3 days prior to starting study intervention, they do not have to be repeated at C1 Day 1 if the participant's condition has not changed.
			Nursing Orders
  	ONC NURSING COMMUNCATION 101	Interval: --	Occurrences: --	Comments:	gBRCA status (optional) 

gBRCA status will be collected, when applicable and if available.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ONC NURSING COMMUNCATION 101	Interval: --	Occurrences: --	Comments:	Targeted physical examination
		  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	OCP (ORAL CARE PLAN)

Participants will be provided an OCP prior to and during neoadjuvant study treatment. Daily before dosing, throughout neoadjuvant treatment, and up to the pre-surgery safety follow-up visit.
			Nursing Orders
  	ONC NURSING COMMUNCATION 101	Interval: --	Occurrences: --	Comments:	AE review.
		  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Prior and concomitant medication review
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Disease assessment.

(medical history, physical exam, clinical signs and symptoms) Every 3 months (± 14 days) from the date of randomization until EoT, at EoT, at the 90-day safety follow-up visit, then every 3 months (± 14 days) until the end of Year 2 from randomization, then every 6 months (± 1 month) for Year 3 to Year 5 from randomization, then annually (12 months [± 1 month]) thereafter until death, withdrawal of consent or end of study.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Mouth and throat diary 

Participants are invited when at home to monitor daily any occurrence of mouth or throat sores and upon occurrence provide additional details, including coping mechanisms.
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Blood pressure, body temperature, heart rate
		  	HEIGHT AND WEIGHT	Interval: --	Occurrences: --			Nursing Orders
  	PULSE OXIMETRY	Interval: --	Occurrences: --			Other
  	PULMONARY FUNCTION TEST	Interval: --	Occurrences: --			Ophthalmology
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Ophthalmologic assessments including but not limited to visual acuity testing, slit lamp examination, intraocular pressure measurement, fundoscopy, and fluorescein staining will be performed by an ophthalmologist, or if unavailable, another licensed eye care provider. Please refer to the Dato-DXd Site Ophthalmologic Assessment Manual for further details.
		  	VISUAL ACUITY SCREENING	Interval: --	Occurrences: --		  	SLIT LAMP PHOTOGRAPHY - OU - BOTH EYES	Interval: --	Occurrences: --		  	FUNDUS PHOTOS - OU - BOTH EYES	Interval: --	Occurrences: --	Comments:	Fundoscopy
			Imaging
  	MAMMO BREAST SCREEN TOMOSYNTHESIS BILATERAL	Interval: --	Occurrences: --	Comments:	Performed at diagnosis.
		  	MRI BREAST WO CONTRAST BILATERAL	Interval: --	Occurrences: --	Comments:	Performed at diagnosis.
			Labs
  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --			Labs
  	GGT	Interval: --	Occurrences: --		  	MAGNESIUM LEVEL	Interval: --	Occurrences: --			Labs
  	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		  	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --			Labs
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	A negative serum pregnancy test must be documented during screening for all FOCBP. If a serum pregnancy test is collected greater than 72 hours prior to randomization, perform a repeat pregnancy test (urine or serum per institutional guideline) within 72 hours before randomization. Perform repeat pregnancy tests (urine or serum per institutional guideline) within 72 hours before treatment at each cycle. A positive urine pregnancy test result mus
t immediately be confirmed using a serum test.
			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --			Labs
  	HCG QUALITATIVE, URINE SCREEN	Interval: --	Occurrences: --			Labs
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Menopausal status Assessments (including FSH, LH, and estradiol);
Menstruation status
			Labs
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Serum or plasma clinical chemistry (including liver function test monitoring) and hematology may be performed more frequently if clinically indicated. If TSH is measured
within 14 days prior to Day 1 (first infusion day), it does not need to be repeated on C1 Day 1. Free T3 or free T4 will only be measured if TSH is abnormal or if there is clinical suspicion of an AE related to the endocrine system. Clinical safety laboratory assessments (clinical chemistry and hematology) are required within 7 days prior to randomization. Table 8
			Labs
  	THYROID STIMULATING HORMONE	Interval: --	Occurrences: --		  	T3	Interval: --	Occurrences: --		  	T4, FREE	Interval: --	Occurrences: --			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --			Labs
  	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --			Pre Infusion Lab
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	(Within 8 hours prior to dose while on therapy)
			Research Labs
  	RESEARCH - MISCELLANEOUS NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	all assessments on dosing days to be performed pre-dose within 2 hours prior to dosing).
			Research Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Research Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Research Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	Surgical specimens at definitive surgery will be collected from all participants for pCR assessment)
			Research Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Procedures
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	ePRO training and setup 

To be conducted for eligible participants only (ie, excluding screening failures) once the participant has been randomized and prior to the first dose of study intervention and any other study procedures. The device should be fully charged, and checked that it is fully functioning, prior to the participant's first dosing visit. The site should ensure the
participant is trained and understands how to use the PRO device prior to the first use. As feasible, site staff should also ensure PRO questionnaires are completed prior to other study procedures, such as collection of laboratory samples, to further minimise bias.
			Nursing Orders
  	ONC NURSING COMMUNICATION 25	Interval: --	Occurrences: --	Comments:	EORTC IL116
		  	ONC NURSING COMMUNICATION 25	Interval: --	Occurrences: --	Comments:	PGIS
		  	ONC NURSING COMMUNICATION 25	Interval: --	Occurrences: --	Comments:	PROMIS Physical Function - Short Form 8c
		  	ONC NURSING COMMUNICATION 25	Interval: --	Occurrences: --	Comments:	EORTC IL172
		  	ONC NURSING COMMUNICATION 25	Interval: --	Occurrences: --	Comments:	EQ-5D-5L
		  	ONC NURSING COMMUNICATION 25	Interval: --	Occurrences: --	Comments:	PGIC
			Nursing Orders
  	ONC NURSING COMMUNICATION 25	Interval: --	Occurrences: --	Comments:	PROMIS Fatigue Short Form 7a
		  	ONC NURSING COMMUNICATION 25	Interval: --	Occurrences: --	Comments:	PRO-CTCAE
		  	ONC NURSING COMMUNICATION 25	Interval: --	Occurrences: --	Comments:	EORTC IL147
		  	ONC NURSING COMMUNICATION 25	Interval: --	Occurrences: --	Comments:	PGI-TT
		  	ONC NURSING COMMUNICATION 25	Interval: --	Occurrences: --	Comments:	EQ-5D-5L
		  	ONC NURSING COMMUNICATION 25	Interval: --	Occurrences: --	Comments:	PGIC
		  	ONC NURSING COMMUNICATION 25	Interval: --	Occurrences: --	Comments:	HOSPAD review 

The site should complete the HOSPAD form at the site at every scheduled clinic visit up to and including the safety follow-up visits. Study mandated visits should not be included as a hospital admission
			Post Infusion Lab
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			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.			Pre-Medications
  	palonosetron (ALOXI) injection 0.25 mg	Dose: 0.25 mg	Route: intravenous	once for 1 dose	Start: S				  	dexAMETHasone (DECADRON) IV 12 mg	Dose: 12 mg	Route: intravenous	once for 1 dose	Start: S				  	fosaprepitant (EMEND) IVPB 150 mg	Dose: 150 mg	Route: intravenous	once over 30 Minutes for 1 dose	Start: S					Chemotherapy
  	pembrolizumab (KEYTRUDA) 200 mg in sodium chloride 0.9% 100 mL IVPB	Dose: 200 mg	Route: intravenous	once over 30 Minutes for 1 dose			Offset: 30 Minutes	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	200 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	92 mL	Yes	Yes				Chemotherapy
  	DOXOrubicin (ADRIAmycin) 60 mg/m2 in sodium chloride 0.9% 100 mL chemo IVPB	Dose: 60 mg/m2	Route: intravenous	once over 30 Minutes for 1 dose			Offset: 60 Minutes	Instructions:	Protect from light; VESICANT	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	DOXORUBICIN 50 MG/25 ML INTRAVENOUS SOLUTION	Medications	60 mg/m2	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	100 mL	Yes	Yes	DEXTROSE 5 % IN WATER (D5W) INTRAVENOUS SOLUTION	QS Base	100 mL	No	Yes			  	cycloPHOSphamide (CYTOXAN) 600 mg/m2 in sodium chloride 0.9% 250 mL chemo IVPB	Dose: 600 mg/m2	Route: intravenous	once over 60 Minutes for 1 dose			Offset: 90 Minutes	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	CYCLOPHOSPHAMIDE 1 GRAM/50 ML INTRAVENOUS POWDER FOR SOLUTION (RECONSTITUTED VIAL)	Medications	600 mg/m2	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	250 mL	Yes	Yes	DEXTROSE 5 % IN WATER (D5W) INTRAVENOUS SOLUTION	QS Base	250 mL	No	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					Supportive Care
  	pegfilgrastim (NEULASTA) on-body injection kit 6 mg	Dose: 6 mg	Route: subcutaneous	once for 1 dose	Start: S			Instructions:	Apply to intact, nonirritated skin on the back of the arm or abdomen (only use the back of the arm if caregiver is available to monitor On-body injection status).			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					
Cycles 2 to 4	Repeat 3 times	Cycle length: 21 days	Day 1	Perform every 1 day x1			Research tolerance: -3/+3 days	Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Inclusion/exclusion criteria.

If screening assessments have been performed within 3 days prior to starting study intervention, they do not have to be repeated at C1 Day 1 if the participant's condition has not changed
		  	ONC NURSING COMMUNCATION 101	Interval: --	Occurrences: --	Comments:	Randomization.

Every effort should be made to minimise the time between randomisation and starting treatment (ie, within 3 business days of randomisation).
		  	ONC NURSING COMMUNCATION 101	Interval: --	Occurrences: --	Comments:	Medical History and current medical conditions.

If screening assessments have been performed within 3 days prior to starting study intervention, they do not have to be repeated at C1 Day 1 if the participant's condition has not changed
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Full physical examination 

If screening assessments have been performed within 3 days prior to starting study intervention, they do not have to be repeated at C1 Day 1 if the participant's condition has not changed.
			Nursing Orders
  	ONC NURSING COMMUNCATION 101	Interval: --	Occurrences: --	Comments:	gBRCA status (optional) 

gBRCA status will be collected, when applicable and if available.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Nursing Orders
  	ONC NURSING COMMUNCATION 101	Interval: --	Occurrences: --	Comments:	Targeted physical examination
		  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	OCP (ORAL CARE PLAN)

Participants will be provided an OCP prior to and during neoadjuvant study treatment. Daily before dosing, throughout neoadjuvant treatment, and up to the pre-surgery safety follow-up visit.
			Nursing Orders
  	ONC NURSING COMMUNCATION 101	Interval: --	Occurrences: --	Comments:	AE review.
		  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Prior and concomitant medication review
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Disease assessment.

(medical history, physical exam, clinical signs and symptoms) Every 3 months (± 14 days) from the date of randomization until EoT, at EoT, at the 90-day safety follow-up visit, then every 3 months (± 14 days) until the end of Year 2 from randomization, then every 6 months (± 1 month) for Year 3 to Year 5 from randomization, then annually (12 months [± 1 month]) thereafter until death, withdrawal of consent or end of study.
			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Mouth and throat diary 

Participants are invited when at home to monitor daily any occurrence of mouth or throat sores and upon occurrence provide additional details, including coping mechanisms.
			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Blood pressure, body temperature, heart rate
		  	HEIGHT AND WEIGHT	Interval: --	Occurrences: --			Nursing Orders
  	PULSE OXIMETRY	Interval: --	Occurrences: --			Other
  	PULMONARY FUNCTION TEST	Interval: --	Occurrences: --			Ophthalmology
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	Ophthalmologic assessments including but not limited to visual acuity testing, slit lamp examination, intraocular pressure measurement, fundoscopy, and fluorescein staining will be performed by an ophthalmologist, or if unavailable, another licensed eye care provider. Please refer to the Dato-DXd Site Ophthalmologic Assessment Manual for further details.
		  	VISUAL ACUITY SCREENING	Interval: --	Occurrences: --		  	SLIT LAMP PHOTOGRAPHY - OU - BOTH EYES	Interval: --	Occurrences: --		  	FUNDUS PHOTOS - OU - BOTH EYES	Interval: --	Occurrences: --	Comments:	Fundoscopy
			Imaging
  	MAMMO BREAST SCREEN TOMOSYNTHESIS BILATERAL	Interval: --	Occurrences: --	Comments:	Performed at diagnosis.
		  	MRI BREAST WO CONTRAST BILATERAL	Interval: --	Occurrences: --	Comments:	Performed at diagnosis.
			Labs
  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --			Labs
  	GGT	Interval: --	Occurrences: --		  	MAGNESIUM LEVEL	Interval: --	Occurrences: --			Labs
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	A negative serum pregnancy test must be documented during screening for all FOCBP. If a serum pregnancy test is collected greater than 72 hours prior to randomization, perform a repeat pregnancy test (urine or serum per institutional guideline) within 72 hours before randomization. Perform repeat pregnancy tests (urine or serum per institutional guideline) within 72 hours before treatment at each cycle. A positive urine pregnancy test result mus
t immediately be confirmed using a serum test.
			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --			Labs
  	HCG QUALITATIVE, URINE SCREEN	Interval: --	Occurrences: --			Labs
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Menopausal status Assessments (including FSH, LH, and estradiol);
Menstruation status
			Labs
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Serum or plasma clinical chemistry (including liver function test monitoring) and hematology may be performed more frequently if clinically indicated. If TSH is measured
within 14 days prior to Day 1 (first infusion day), it does not need to be repeated on C1 Day 1. Free T3 or free T4 will only be measured if TSH is abnormal or if there is clinical suspicion of an AE related to the endocrine system. Clinical safety laboratory assessments (clinical chemistry and hematology) are required within 7 days prior to randomization. Table 8
			Labs
  	THYROID STIMULATING HORMONE	Interval: --	Occurrences: --		  	T3	Interval: --	Occurrences: --		  	T4, FREE	Interval: --	Occurrences: --			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --			Labs
  	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --			Pre Infusion Lab
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	(Within 8 hours prior to dose while on therapy)
			Research Labs
  	RESEARCH - MISCELLANEOUS NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	all assessments on dosing days to be performed pre-dose within 2 hours prior to dosing).
			Research Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Research Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Research Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	Surgical specimens at definitive surgery will be collected from all participants for pCR assessment)
			Research Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Procedures
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Nursing Orders
  	ONC NURSING COMMUNICATION	Interval: --	Occurrences: --	Comments:	ePRO training and setup 

To be conducted for eligible participants only (ie, excluding screening failures) once the participant has been randomized and prior to the first dose of study intervention and any other study procedures. The device should be fully charged, and checked that it is fully functioning, prior to the participant's first dosing visit. The site should ensure the
participant is trained and understands how to use the PRO device prior to the first use. As feasible, site staff should also ensure PRO questionnaires are completed prior to other study procedures, such as collection of laboratory samples, to further minimise bias.
			Nursing Orders
  	ONC NURSING COMMUNICATION 25	Interval: --	Occurrences: --	Comments:	EORTC IL116
		  	ONC NURSING COMMUNICATION 25	Interval: --	Occurrences: --	Comments:	PGIS
		  	ONC NURSING COMMUNICATION 25	Interval: --	Occurrences: --	Comments:	PROMIS Physical Function - Short Form 8c
		  	ONC NURSING COMMUNICATION 25	Interval: --	Occurrences: --	Comments:	EORTC IL172
		  	ONC NURSING COMMUNICATION 25	Interval: --	Occurrences: --	Comments:	EQ-5D-5L
		  	ONC NURSING COMMUNICATION 25	Interval: --	Occurrences: --	Comments:	PGIC
			Nursing Orders
  	ONC NURSING COMMUNICATION 25	Interval: --	Occurrences: --	Comments:	PROMIS Fatigue Short Form 7a
		  	ONC NURSING COMMUNICATION 25	Interval: --	Occurrences: --	Comments:	PRO-CTCAE
		  	ONC NURSING COMMUNICATION 25	Interval: --	Occurrences: --	Comments:	EORTC IL147
		  	ONC NURSING COMMUNICATION 25	Interval: --	Occurrences: --	Comments:	PGI-TT
		  	ONC NURSING COMMUNICATION 25	Interval: --	Occurrences: --	Comments:	EQ-5D-5L
		  	ONC NURSING COMMUNICATION 25	Interval: --	Occurrences: --	Comments:	PGIC
		  	ONC NURSING COMMUNICATION 25	Interval: --	Occurrences: --	Comments:	HOSPAD review 

The site should complete the HOSPAD form at the site at every scheduled clinic visit up to and including the safety follow-up visits. Study mandated visits should not be included as a hospital admission
			Post Infusion Lab
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			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.			Pre-Medications
  	palonosetron (ALOXI) injection 0.25 mg	Dose: 0.25 mg	Route: intravenous	once for 1 dose	Start: S				  	dexAMETHasone (DECADRON) IV 12 mg	Dose: 12 mg	Route: intravenous	once for 1 dose	Start: S				  	fosaprepitant (EMEND) IVPB 150 mg	Dose: 150 mg	Route: intravenous	once over 30 Minutes for 1 dose	Start: S					Chemotherapy
  	pembrolizumab (KEYTRUDA) 200 mg in sodium chloride 0.9% 100 mL IVPB	Dose: 200 mg	Route: intravenous	once over 30 Minutes for 1 dose			Offset: 30 Minutes	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	200 mg	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	92 mL	Yes	Yes				Chemotherapy
  	DOXOrubicin (ADRIAmycin) 60 mg/m2 in sodium chloride 0.9% 100 mL chemo IVPB	Dose: 60 mg/m2	Route: intravenous	once over 30 Minutes for 1 dose			Offset: 60 Minutes	Instructions:	Protect from light; VESICANT	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	DOXORUBICIN 50 MG/25 ML INTRAVENOUS SOLUTION	Medications	60 mg/m2	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	100 mL	Yes	Yes	DEXTROSE 5 % IN WATER (D5W) INTRAVENOUS SOLUTION	QS Base	100 mL	No	Yes			  	cycloPHOSphamide (CYTOXAN) 600 mg/m2 in sodium chloride 0.9% 250 mL chemo IVPB	Dose: 600 mg/m2	Route: intravenous	once over 60 Minutes for 1 dose			Offset: 90 Minutes	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	CYCLOPHOSPHAMIDE 1 GRAM/50 ML INTRAVENOUS POWDER FOR SOLUTION (RECONSTITUTED VIAL)	Medications	600 mg/m2	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	250 mL	Yes	Yes	DEXTROSE 5 % IN WATER (D5W) INTRAVENOUS SOLUTION	QS Base	250 mL	No	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					Supportive Care
  	pegfilgrastim (NEULASTA) on-body injection kit 6 mg	Dose: 6 mg	Route: subcutaneous	once for 1 dose	Start: S			Instructions:	Apply to intact, nonirritated skin on the back of the arm or abdomen (only use the back of the arm if caregiver is available to monitor On-body injection status).			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