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Phase 2 Trial of Pertuzumab and Trastuzumab With Weekly Paclitaxel and Chemotherapy for HER2 Positive Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01855828
Recruitment Status : Completed
First Posted : May 17, 2013
Results First Posted : March 31, 2020
Last Update Posted : March 31, 2020
Genentech, Inc.
Information provided by (Responsible Party):
Yale University

Brief Summary:
The main goal of this clinical trial is to test if adding pertuzumab (Perjeta), improves the anticancer activity of the combination chemotherapy regimen of trastuzumab (Herceptin) concomitant with paclitaxel, 5-fluorouracil, epirubicin, and cyclophosphamide (T-FEC). The study will also test the safety of this therapy.

Condition or disease Intervention/treatment Phase
Her2-Positive Breast Cancer Drug: Pertuzumab Drug: Trastuzumab Drug: Paclitaxel Drug: 5-fluorouracil Drug: Epirubicin Drug: Cyclophosphamide Phase 2

Detailed Description:
Subjects will receive 6 months of T-FEC chemotherapy concomitant with trastuzumab and pertuzumab before surgery. Subsequently, subjects will undergo surgery to remove any cancer from the breast and axillary lymph nodes that may have survived the chemotherapy. It is expected that the majority of women will have no viable cancer left in the breast or lymph nodes by the time all chemotherapy is completed.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Single Arm, Neoadjuvant, Phase II Trial of Pertuzumab and Trastuzumab Administered Concomitantly With Weekly Paclitaxel and FEC for Clinical Stage I-II HER2-Positive Breast Cancer
Study Start Date : September 2013
Actual Primary Completion Date : August 2018
Actual Study Completion Date : August 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: 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).
Drug: Pertuzumab
First dose is 840mg, maintenance dose is 420mg. Pertuzumab will be administered once every 3 weeks for 24 weeks (8 doses total)
Other Name: Perjeta

Drug: 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).

Other Name: Herceptin

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

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

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

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

Primary Outcome Measures :
  1. Proportion of Participants With a Pathologic Complete Response Rate [ Time Frame: 20 weeks ]
    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.

Secondary Outcome Measures :
  1. Cardiac Safety [ Time Frame: Up to 1 year post surgery ]
    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.

  2. Count of Patients With Clinical Response [ Time Frame: Up to 28 weeks ]
    To assess clinical response according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, the number of patients are presented with a clinical response.

  3. Residual Cancer Burden Score [ Time Frame: Up to 28 weeks ]
    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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01855828

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United States, Connecticut
Yale University Smilow Cancer Hospital
New Haven, Connecticut, United States, 06520
Sponsors and Collaborators
Yale University
Genentech, Inc.
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Principal Investigator: Lajos Pusztai, MD Yale University
  Study Documents (Full-Text)

Documents provided by Yale University:
Informed Consent Form  [PDF] August 7, 2017

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Responsible Party: Yale University Identifier: NCT01855828    
Other Study ID Numbers: 1305012136
First Posted: May 17, 2013    Key Record Dates
Results First Posted: March 31, 2020
Last Update Posted: March 31, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antineoplastic Agents, Immunological
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors