Phase 2 Trial of Pertuzumab and Trastuzumab With Weekly P... | NCT01855828

NCT01855828

Status Module

Sponsor/Collaborators Module

Name	Class
Genentech, Inc.	INDUSTRY

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Chemo plus Pertuzumab,Trastuzumab	Experimental	During weeks 1-12, patients will receive pertuzumab, trastuzumab, and paclitaxel at the same time; during weeks 13-24 patients will receive pertuzumab and trastuzumab at the same time with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC).	Drug: Pertuzumab Drug: Trastuzumab Drug: Paclitaxel Drug: 5-fluorouracil Drug: Epirubicin Drug: Cyclophosphamide

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Pertuzumab	Drug	First dose is 840mg, maintenance dose is 420mg. Pertuzumab will be administered once every 3 weeks for 24 weeks (8 doses total)	Chemo plus Pertuzumab,Trastuzumab

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Proportion of Participants With a Pathologic Complete Response Rate	To estimate the pathologic complete response rate (pCR) when pertuzumab is added to weekly trastuzumab/paclitaxel followed by trastuzumab/5-fluorouracil, epirubicin and cyclophosphamide neoadjuvant chemotherapy in HER2-positive breast cancer. This study will assess pCR rates separately in ER+ and ER- cancers. Pathologic complete response is defined as no evidence of viable invasive tumor cells at the primary tumor site and axillary lymph nodes in the surgical specimen. Residual Disease (RD) is defined as: Any invasive cancer in the breast or axillary lymph nodes in the surgical specimen.	20 weeks

Secondary Outcomes

Measure	Description	Time Frame
Cardiac Safety	To assess the safety of the regimen, cardiac safety was measured by rates of clinically symptomatic congestive heart failure, asymptomatic decrease in LVEF >10%, and decrease of LVEF below normal level. This was assessed up to 1 year following surgery.	Up to 1 year post surgery
Count of Patients With Clinical Response

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

- Patients with histologically confirmed stage I-III, HER2-positive invasive breast cancer for which adjuvant/neoadjuvant chemotherapy is indicated based on physician judgment following NCCN practice guidelines.

HER2 overexpression or amplification will be based on local test results and is defined as either:

(i) IHC staining of 3+ (uniform, intense membrane staining) in greater than or equal to 10% of invasive tumor cells or, (ii) Fluorescent in situ hybridization (FISH) result of more than six HER2 gene copies per nucleus or, (iii) FISH ratio (HER2 gene signals to chromosome 17 signals) of greater than or equal to 2.0.

Patients with synchronous bilateral breast cancers are eligible if at least one of the tumors is HER2-positive.
Left Ventricular Ejection Fraction (LVEF) greater or equal to 50% at baseline as determined by either ECHO or MUGA, or within the institution's normal limits.
Women of childbearing potential must have a negative pregnancy test (serum or urine beta HCG) prior to initiation of chemotherapy. Both female and male breast cancer patients who are sexually active have to agree to practice contraception while participating in the trial and for 3 month after completion of therapy.
Adequate bone marrow function as indicated by the following:
ANC greater than or equal to 1500/uL
Platelets greater than or equal to 100,000/uL
Hemoglobin greater than or equal to 10 g/dL
Adequate renal function, as indicated by creatinine less than or equal to 1.5 times upper limit of normal (ULN)
Adequate liver function, as indicated by bilirubin less than or equal to 1.5 X ULN and AST or ALT less than or equal to 2x ULN.
Signed informed consent.

Exclusion Criteria:

Patients will be excluded from the study based on any of the following criteria:

Patients who underwent partial excisional biopsy, lumpectomy, segmental mastectomy, modified radical mastectomy or sentinel node biopsy and, therefore cannot be assessed for pathologic response accurately.
Patients who are high risk for developing the following anthracycline, paclitaxel, trastuzumab or pertuzumab related toxicities including:

History of congestive heart failure, myocardial infarction or cardiomyopathy, uncontrolled hypertension despite adequate medications Pre-existing peripheral neuropathy > grade 3 Prior anthracycline therapy Known hypersensitivity to any of the study medications Patients older than age 65 due to increased risk of cardiotoxicity

Active infection requiring systemic antibiotic therapy.
Pregnant or lactating women

Contacts/Locations Module

Name	Affiliation	Role
Lajos Pusztai, MD	Yale University	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Yale University Smilow Cancer Hospital		New Haven	Connecticut	06520	United States

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Chemo Plus Pertuzumab,Trastuzumab	During weeks 1-12, patients will receive pertuzumab, trastuzumab, and paclitaxel at the same time; during weeks 13-24 patients will receive pertuzumab and trastuzumab at the same time with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC). Pertuzumab: First dose is 840mg, maintenance dose is 420mg. Pertuzumab will be administered once every 3 weeks for 24 weeks (8 doses total) Trastuzumab: For weeks 1-12, first dose is 4 mg/kg, maintenance dose is 2 mg/kg administered every week (12 doses total). For weeks 13-24, dose is 6mg/kg administered every 3 weeks (4 doses total). Paclitaxel: Administered at 80mg/m2 every week from week 1 to 12 (12 doses total). 5-fluorouracil: Administered at 500 mg/m2 for every 3 weeks during weeks 13-24 (4 doses total). Epirubicin: Administered at 75mg/m2 every 3 weeks during weeks 13-24 (4 doses total). Cyclophosphamide: Administered at 500mg/m2 for every 3 weeks during weeks 13-24 (4 doses total).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
ICF	No	No	Yes	Informed Consent Form	Aug 7, 2017	Feb 27, 2020

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

No data available

No data is available for this block.

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Chemo Plus Pertuzumab,Trastuzumab	During weeks 1-12, patients will receive pertuzumab, trastuzumab, and paclitaxel at the same time; during weeks 13-24 patients will receive pertuzumab and trastuzumab at the same time with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC). Pertuzumab: First dose is 840mg, maintenance dose is 420mg. Pertuzumab will be administered once every 3 weeks for 24 weeks (8 doses total) Trastuzumab: For weeks 1-12, first dose is 4 mg/kg, maintenance dose is 2 mg/kg administered every week (12 doses total). For weeks 13-24, dose is 6mg/kg administered every 3 weeks (4 doses total). Paclitaxel: Administered at 80mg/m2 every week from week 1 to 12 (12 doses total). 5-fluorouracil: Administered at 500 mg/m2 for every 3 weeks during weeks 13-24 (4 doses total). Epirubicin: Administered at 75mg/m2 every 3 weeks during weeks 13-24 (4 doses total). Cyclophosphamide: Administered at 500mg/m2 for every 3 weeks during weeks 13-24 (4 doses total).

Units	Counts
Participants	BG00050

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Median

Full Range

years

Title

Denominators

Categories

Title	Measurements
	BG00051(24 to 63)

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00050
Male	BG0000

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Race/Ethnicity

Title	Measurements
White	BG00036
African American	BG0004

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG00050

Hormone receptor status

Receptor status retrieved from the subjects diagnostic pathology report.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Estrogen Receptor + / Progesterone Receptor +	BG00020
Estrogen Receptor + / Progesterone Receptor -	BG000

HER2 status

Fluorescence in situ hybridization (FISH) and Immunohistochemistry (IHC) are tests used to detect breast cancer genetically. A positive FISH test and ICH status of 3+ are markers of HER2 status. These data were retrieved from the subjects' diagnostic pathology report and demonstrate the manner in which these patients were diagnosed.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Fluorescence in situ hybridization (FISH) positive	BG00027
Immunohistochemistry (IHC) 3+	BG000

Clinical Tumor Status

Baseline clinical staging

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
T1: Tumor is 2 cm or smaller	BG00018
T2: Tumor is larger than 2 cm, but no larger than	BG000

Type of surgery

The type of surgery describes the manner in which the patients' breast cancer was addressed surgically.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Mastectomy	BG00035
Breast conserving surgery	BG000

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Proportion of Participants With a Pathologic Complete Response Rate

To estimate the pathologic complete response rate (pCR) when pertuzumab is added to weekly trastuzumab/paclitaxel followed by trastuzumab/5-fluorouracil, epirubicin and cyclophosphamide neoadjuvant chemotherapy in HER2-positive breast cancer. This study will assess pCR rates separately in ER+ and ER- cancers. Pathologic complete response is defined as no evidence of viable invasive tumor cells at the primary tumor site and axillary lymph nodes in the surgical specimen. Residual Disease (RD) is defined as: Any invasive cancer in the breast or axillary lymph nodes in the surgical specimen.

For ER-negative cancers, the maximum sample size was set to n = 25 and the regimen would be considered of interest if > 20 patients achieve pCR. For ER-positive patients, the maximum sample size for the ER-positive cohort was set to 39 and the regimen would be considered of interest in this subgroup if > 23 patients achieve pCR.

Posted

Number

95% Confidence Interval

proportion of participants

20 weeks

ID	Title	Description
OG000	Chemo Plus Pertuzumab,Trastuzumab	During weeks 1-12, patients will receive pertuzumab, trastuzumab, and paclitaxel at the same time; during weeks 13-24 patients will receive pertuzumab and trastuzumab at the same time with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC). Pertuzumab: First dose is 840mg, maintenance dose is 420mg. Pertuzumab will be administered once every 3 weeks for 24 weeks (8 doses total) Trastuzumab: For weeks 1-12, first dose is 4 mg/kg, maintenance dose is 2 mg/kg administered every week (12 doses total). For weeks 13-24, dose is 6mg/kg administered every 3 weeks (4 doses total). Paclitaxel: Administered at 80mg/m2 every week from week 1 to 12 (12 doses total). 5-fluorouracil: Administered at 500 mg/m2 for every 3 weeks during weeks 13-24 (4 doses total). Epirubicin: Administered at 75mg/m2 every 3 weeks during weeks 13-24 (4 doses total). Cyclophosphamide: Administered at 500mg/m2 for every 3 weeks during weeks 13-24 (4 doses total).

Units	Counts
Participants	OG00048

Title

Denominators

Categories

HR Positive

- ParticipantsOG00023

Title	Measurements
	OG000.26(.13 to .46)

HR Negative

- ParticipantsOG000

Secondary

Cardiac Safety

To assess the safety of the regimen, cardiac safety was measured by rates of clinically symptomatic congestive heart failure, asymptomatic decrease in LVEF >10%, and decrease of LVEF below normal level. This was assessed up to 1 year following surgery.

All patients are assessed in each arm.

Posted

Count of Participants

Participants

Up to 1 year post surgery

ID	Title	Description
OG000	Chemo Plus Pertuzumab,Trastuzumab-symptomatic Congestive Heart	During weeks 1-12, patients will receive pertuzumab, trastuzumab, and paclitaxel at the same time; during weeks 13-24 patients will receive pertuzumab and trastuzumab at the same time with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC). Pertuzumab: First dose is 840mg, maintenance dose is 420mg. Pertuzumab will be administered once every 3 weeks for 24 weeks (8 doses total) Trastuzumab: For weeks 1-12, first dose is 4 mg/kg, maintenance dose is 2 mg/kg administered every week (12 doses total). For weeks 13-24, dose is 6mg/kg administered every 3 weeks (4 doses total). Paclitaxel: Administered at 80mg/m2 every week from week 1 to 12 (12 doses total). 5-fluorouracil: Administered at 500 mg/m2 for every 3 weeks during weeks 13-24 (4 doses total). Epirubicin: Administered at 75mg/m2 every 3 weeks during weeks 13-24 (4 doses total). Cyclophosphamide: Administered at 500mg/m2 for every 3 weeks during weeks 13-24 (4 doses total).
OG001	Chemo Plus Pertuzumab,Trastuzumab-asympomatic Decrease in LVEF

Secondary

Count of Patients With Clinical Response

To assess clinical response according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, the number of patients are presented with a clinical response.

All patients are assessed by HR-positive or HR-negative status.

Posted

Count of Participants

Participants

Up to 28 weeks

ID	Title	Description
OG000	Chemo Plus Pertuzumab,Trastuzumab HR-positive	During weeks 1-12, patients will receive pertuzumab, trastuzumab, and paclitaxel at the same time; during weeks 13-24 patients will receive pertuzumab and trastuzumab at the same time with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC). Pertuzumab: First dose is 840mg, maintenance dose is 420mg. Pertuzumab will be administered once every 3 weeks for 24 weeks (8 doses total) Trastuzumab: For weeks 1-12, first dose is 4 mg/kg, maintenance dose is 2 mg/kg administered every week (12 doses total). For weeks 13-24, dose is 6mg/kg administered every 3 weeks (4 doses total). Paclitaxel: Administered at 80mg/m2 every week from week 1 to 12 (12 doses total). 5-fluorouracil: Administered at 500 mg/m2 for every 3 weeks during weeks 13-24 (4 doses total). Epirubicin: Administered at 75mg/m2 every 3 weeks during weeks 13-24 (4 doses total). Cyclophosphamide: Administered at 500mg/m2 for every 3 weeks during weeks 13-24 (4 doses total).
OG001	Chemo Plus Pertuzumab,Trastuzumab HR-negative	During weeks 1-12, patients will receive pertuzumab, trastuzumab, and paclitaxel at the same time; during weeks 13-24 patients will receive pertuzumab and trastuzumab at the same time with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC). Pertuzumab: First dose is 840mg, maintenance dose is 420mg. Pertuzumab will be administered once every 3 weeks for 24 weeks (8 doses total) Trastuzumab: For weeks 1-12, first dose is 4 mg/kg, maintenance dose is 2 mg/kg administered every week (12 doses total). For weeks 13-24, dose is 6mg/kg administered every 3 weeks (4 doses total). Paclitaxel: Administered at 80mg/m2 every week from week 1 to 12 (12 doses total). 5-fluorouracil: Administered at 500 mg/m2 for every 3 weeks during weeks 13-24 (4 doses total). Epirubicin: Administered at 75mg/m2 every 3 weeks during weeks 13-24 (4 doses total). Cyclophosphamide: Administered at 500mg/m2 for every 3 weeks during weeks 13-24 (4 doses total).

Secondary

Residual Cancer Burden Score

To assess cancer burben, the Residual Cancer Burden (RCB) score was used. This score has a range of 0 - III, where III (3) is the worst level of burden.

Total participants that were analyzed for this score (n=43).

Posted

Count of Participants

Participants

Up to 28 weeks

ID	Title	Description
OG000	Chemo Plus Pertuzumab,Trastuzumab	During weeks 1-12, patients will receive pertuzumab, trastuzumab, and paclitaxel at the same time; during weeks 13-24 patients will receive pertuzumab and trastuzumab at the same time with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC). Pertuzumab: First dose is 840mg, maintenance dose is 420mg. Pertuzumab will be administered once every 3 weeks for 24 weeks (8 doses total) Trastuzumab: For weeks 1-12, first dose is 4 mg/kg, maintenance dose is 2 mg/kg administered every week (12 doses total). For weeks 13-24, dose is 6mg/kg administered every 3 weeks (4 doses total). Paclitaxel: Administered at 80mg/m2 every week from week 1 to 12 (12 doses total). 5-fluorouracil: Administered at 500 mg/m2 for every 3 weeks during weeks 13-24 (4 doses total). Epirubicin: Administered at 75mg/m2 every 3 weeks during weeks 13-24 (4 doses total). Cyclophosphamide: Administered at 500mg/m2 for every 3 weeks during weeks 13-24 (4 doses total).

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Chemo Plus Pertuzumab,Trastuzumab	During weeks 1-12, patients will receive pertuzumab, trastuzumab, and paclitaxel at the same time; during weeks 13-24 patients will receive pertuzumab and trastuzumab at the same time with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC). Pertuzumab: First dose is 840mg, maintenance dose is 420mg. Pertuzumab will be administered once every 3 weeks for 24 weeks (8 doses total) Trastuzumab: For weeks 1-12, first dose is 4 mg/kg, maintenance dose is 2 mg/kg administered every week (12 doses total). For weeks 13-24, dose is 6mg/kg administered every 3 weeks (4 doses total). Paclitaxel: Administered at 80mg/m2 every week from week 1 to 12 (12 doses total). 5-fluorouracil: Administered at 500 mg/m2 for every 3 weeks during weeks 13-24 (4 doses total). Epirubicin: Administered at 75mg/m2 every 3 weeks during weeks 13-24 (4 doses total). Cyclophosphamide: Administered at 500mg/m2 for every 3 weeks during weeks 13-24 (4 doses total).	0	50	6	50	50	50

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Catheter related infection	Infections and infestations	CTCAEv4.	Systematic Assessment		EG0002 events2 affected50 at risk
Ventricular tachycardia	Cardiac disorders	CTCAEv4.	Systematic Assessment		EG0001 events1 affected50 at risk
Fever	General disorders	CTCAEv4.	Systematic Assessment	event related to surgery complications	EG0001 events1 affected50 at risk
Suicidal ideation	Psychiatric disorders	CTCAEv4.	Non-systematic Assessment	Underlying condition of bi polar disorder	EG0001 events1 affected50 at risk
Flu like symptoms	General disorders	CTCAEv4.	Systematic Assessment		EG0001 events1 affected50 at risk
Thromboembolic event	Vascular disorders	CTCAEv4.	Systematic Assessment		EG0001 events1 affected50 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	CTCAEv4.	Non-systematic Assessment	EG00065 events36 affected50 at risk
Febrile neutropenia	Blood and lymphatic system disorders	CTCAEv4.	Non-systematic Assessment	EG0003 events3 affected50 at risk
Palpitations	Cardiac disorders	CTCAEv4.	Non-systematic Assessment	EG0005 events3 affected50 at risk
Blurred vision	Eye disorders	CTCAEv4.	Non-systematic Assessment	EG0005 events5 affected50 at risk
Watering eyes	Eye disorders	CTCAEv4.	Non-systematic Assessment	EG00013 events12 affected50 at risk
Abdominal pain	Gastrointestinal disorders	CTCAEv4.	Non-systematic Assessment	EG00012 events10 affected50 at risk
Constipation	Gastrointestinal disorders	CTCAEv4.	Non-systematic Assessment	EG00015 events14 affected50 at risk
Diarrhea	Gastrointestinal disorders	CTCAEv4.	Non-systematic Assessment	EG000110 events45 affected50 at risk
Dry mouth	Gastrointestinal disorders	CTCAEv4.	Non-systematic Assessment	EG0006 events5 affected50 at risk
Dyspepsia	Gastrointestinal disorders	CTCAEv4.	Non-systematic Assessment	EG0008 events7 affected50 at risk
Gastroesophageal reflux disease	Gastrointestinal disorders	CTCAEv4.	Non-systematic Assessment	EG00012 events10 affected50 at risk
Mucositis oral	Gastrointestinal disorders	CTCAEv4.	Non-systematic Assessment	EG00033 events19 affected50 at risk
Nausea	Gastrointestinal disorders	CTCAEv4.	Non-systematic Assessment	EG00067 events41 affected50 at risk
Stomach pain	Gastrointestinal disorders	CTCAEv4.	Non-systematic Assessment	EG0003 events3 affected50 at risk
Vomiting	Gastrointestinal disorders	CTCAEv4.	Non-systematic Assessment	EG00018 events13 affected50 at risk
Edema limbs	General disorders	CTCAEv4.	Non-systematic Assessment	EG00010 events8 affected50 at risk
Fatigue	General disorders	CTCAEv4.	Non-systematic Assessment	EG00059 events43 affected50 at risk
Infusion related reaction	General disorders	CTCAEv4.	Non-systematic Assessment	EG0004 events3 affected50 at risk
Pain	General disorders	CTCAEv4.	Non-systematic Assessment	EG00049 events27 affected50 at risk
Allergic reaction	Immune system disorders	CTCAEv4.	Non-systematic Assessment	EG0005 events4 affected50 at risk
Nail infection	Infections and infestations	CTCAEv4.	Non-systematic Assessment	EG0006 events6 affected50 at risk
Skin infection	Infections and infestations	CTCAEv4.	Non-systematic Assessment	EG0004 events4 affected50 at risk
Upper respiratory infection	Infections and infestations	CTCAEv4.	Non-systematic Assessment	EG0004 events4 affected50 at risk
Urinary tract infection	Infections and infestations	CTCAEv4.	Non-systematic Assessment	EG0006 events6 affected50 at risk
Alanine aminotransferase increased	Investigations	CTCAEv4.	Non-systematic Assessment	EG00052 events27 affected50 at risk
Alkaline phosphatase increased	Investigations	CTCAEv4.	Non-systematic Assessment	EG0008 events6 affected50 at risk
Aspartate aminotransferase increased	Investigations	CTCAEv4.	Non-systematic Assessment	EG00020 events16 affected50 at risk
Neutrophil count decreased	Investigations	CTCAEv4.	Non-systematic Assessment	EG00021 events13 affected50 at risk
Weight loss	Investigations	CTCAEv4.	Non-systematic Assessment	EG0004 events4 affected50 at risk
White blood cell decreased	Investigations	CTCAEv4.	Non-systematic Assessment	EG00047 events21 affected50 at risk
Anorexia	Metabolism and nutrition disorders	CTCAEv4.	Non-systematic Assessment	EG0007 events5 affected50 at risk
Hypoalbuminemia	Metabolism and nutrition disorders	CTCAEv4.	Non-systematic Assessment	EG0003 events3 affected50 at risk
Hypocalcemia	Metabolism and nutrition disorders	CTCAEv4.	Non-systematic Assessment	EG00013 events8 affected50 at risk
Hypokalemia	Metabolism and nutrition disorders	CTCAEv4.	Non-systematic Assessment	EG00019 events10 affected50 at risk
Hypomagnesemia	Metabolism and nutrition disorders	CTCAEv4.	Non-systematic Assessment	EG0003 events3 affected50 at risk
Hyponatremia	Metabolism and nutrition disorders	CTCAEv4.	Non-systematic Assessment	EG0005 events3 affected50 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	CTCAEv4.	Non-systematic Assessment	EG0005 events5 affected50 at risk
Back pain	Musculoskeletal and connective tissue disorders	CTCAEv4.	Non-systematic Assessment	EG0009 events6 affected50 at risk
Bone pain	Musculoskeletal and connective tissue disorders	CTCAEv4.	Non-systematic Assessment	EG0007 events5 affected50 at risk
Myalgia	Musculoskeletal and connective tissue disorders	CTCAEv4.	Non-systematic Assessment	EG0007 events7 affected50 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	CTCAEv4.	Non-systematic Assessment	EG0007 events7 affected50 at risk
Dizziness	Nervous system disorders	CTCAEv4.	Non-systematic Assessment	EG00012 events10 affected50 at risk
Dysgeusia	Nervous system disorders	CTCAEv4.	Non-systematic Assessment	EG00011 events10 affected50 at risk
Headache	Nervous system disorders	CTCAEv4.	Non-systematic Assessment	EG00020 events16 affected50 at risk
Paresthesia	Nervous system disorders	CTCAEv4.	Non-systematic Assessment	EG0005 events4 affected50 at risk
Peripheral motor neuropathy	Nervous system disorders	CTCAEv4.	Non-systematic Assessment	EG0008 events7 affected50 at risk
Peripheral sensory neuropathy	Nervous system disorders	CTCAEv4.	Non-systematic Assessment	EG00034 events25 affected50 at risk
Anxiety	Psychiatric disorders	CTCAEv4.	Non-systematic Assessment	EG00010 events8 affected50 at risk
Insomnia	Psychiatric disorders	CTCAEv4.	Non-systematic Assessment	EG00021 events18 affected50 at risk
Urinary frequency	Renal and urinary disorders	CTCAEv4.	Non-systematic Assessment	EG0003 events3 affected50 at risk
Urinary tract pain	Renal and urinary disorders	CTCAEv4.	Non-systematic Assessment	EG0006 events4 affected50 at risk
Breast pain	Reproductive system and breast disorders	CTCAEv4.	Non-systematic Assessment	EG0006 events5 affected50 at risk
Allergic rhinitis	Respiratory, thoracic and mediastinal disorders	CTCAEv4.	Non-systematic Assessment	EG00022 events19 affected50 at risk
Cough	Respiratory, thoracic and mediastinal disorders	CTCAEv4.	Non-systematic Assessment	EG00010 events9 affected50 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	CTCAEv4.	Non-systematic Assessment	EG00010 events10 affected50 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	CTCAEv4.	Non-systematic Assessment	EG00040 events35 affected50 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	CTCAEv4.	Non-systematic Assessment	EG00010 events8 affected50 at risk
Sore throat	Respiratory, thoracic and mediastinal disorders	CTCAEv4.	Non-systematic Assessment	EG0006 events6 affected50 at risk
Alopecia	Skin and subcutaneous tissue disorders	CTCAEv4.	Non-systematic Assessment	EG00050 events38 affected50 at risk
Dry skin	Skin and subcutaneous tissue disorders	CTCAEv4.	Non-systematic Assessment	EG0008 events8 affected50 at risk
Nail discoloration	Skin and subcutaneous tissue disorders	CTCAEv4.	Non-systematic Assessment	EG00020 events18 affected50 at risk
Pruritus	Skin and subcutaneous tissue disorders	CTCAEv4.	Non-systematic Assessment	EG0008 events7 affected50 at risk
Rash acneiform	Skin and subcutaneous tissue disorders	CTCAEv4.	Non-systematic Assessment	EG00024 events19 affected50 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	CTCAEv4.	Non-systematic Assessment	EG00024 events21 affected50 at risk
Scalp pain	Skin and subcutaneous tissue disorders	CTCAEv4.	Non-systematic Assessment	EG0003 events3 affected50 at risk
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	CTCAEv4.	Non-systematic Assessment	EG0005 events4 affected50 at risk
Flushing	Vascular disorders	CTCAEv4.	Non-systematic Assessment	EG0003 events3 affected50 at risk
Hot flashes	Vascular disorders	CTCAEv4.	Non-systematic Assessment	EG00022 events20 affected50 at risk
Hypertension	Vascular disorders	CTCAEv4.	Non-systematic Assessment	EG00016 events7 affected50 at risk

ID	Term
C485206	pertuzumab
D000068878	Trastuzumab
D017239	Paclitaxel
D005472	Fluorouracil
D015251	Epirubicin
D003520	Cyclophosphamide

Ancestor Terms

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D004224	Diterpenes
D013729	Terpenes
D014498	Uracil
D011744	Pyrimidinones
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D004317	Doxorubicin
D003630	Daunorubicin
D018943	Anthracyclines
D009279	Naphthacenes
D011084	Polycyclic Aromatic Hydrocarbons
D006841	Hydrocarbons, Aromatic
D011083	Polycyclic Compounds
D000617	Aminoglycosides
D006027	Glycosides
D002241	Carbohydrates
D010752	Phosphoramide Mustards
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D063088	Phosphoramides
D009943	Organophosphorus Compounds

During weeks 1-12, patients will receive pertuzumab, trastuzumab, and paclitaxel at the same time; during weeks 13-24 patients will receive pertuzumab and trastuzumab at the same time with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC).

Pertuzumab: First dose is 840mg, maintenance dose is 420mg. Pertuzumab will be administered once every 3 weeks for 24 weeks (8 doses total)

Trastuzumab: For weeks 1-12, first dose is 4 mg/kg, maintenance dose is 2 mg/kg administered every week (12 doses total).

For weeks 13-24, dose is 6mg/kg administered every 3 weeks (4 doses total).

Paclitaxel: Administered at 80mg/m2 every week from week 1 to 12 (12 doses total).

5-fluorouracil: Administered at 500 mg/m2 for every 3 weeks during weeks 13-24 (4 doses total).

Epirubicin: Administered at 75mg/m2 every 3 weeks during weeks 13-24 (4 doses total).

Cyclophosphamide: Administered at 500mg/m2 for every 3 weeks during weeks 13-24 (4 doses total).