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

NCT ID: NCT01855828

Last Updated: 2020-03-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-30
• Study Completion Date: 2018-08-31

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.

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.

Conditions

Her2-Positive Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

Pertuzumab

Intervention Type: DRUG

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

Trastuzumab

Intervention Type: DRUG

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

Intervention Type: DRUG

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

5-fluorouracil

Intervention Type: DRUG

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

Epirubicin

Intervention Type: DRUG

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

Cyclophosphamide

Intervention Type: DRUG

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

Interventions

Pertuzumab

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

Intervention Type: 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).

Intervention Type: DRUG

Paclitaxel

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

Intervention Type: DRUG

5-fluorouracil

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

Intervention Type: DRUG

Epirubicin

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

Intervention Type: DRUG

Cyclophosphamide

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

Intervention Type: DRUG

Other Intervention Names

Perjeta; Herceptin; Taxol; 5-FU; Ellence; Cytoxan

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lajos Pusztai, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Yale University Smilow Cancer Hospital

New Haven, Connecticut, United States

Countries

United States

Provided Documents

Document Type: Informed Consent Form

View Document

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1305012136

Identifier Type: -

Identifier Source: org_study_id