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

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

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.

Study Overview

• Status: Completed
• Conditions: Her2-Positive Breast Cancer
• Intervention / Treatment: Drug: Pertuzumab; Drug: Trastuzumab; Drug: Paclitaxel; Drug: 5-fluorouracil; Drug: Epirubicin; Drug: Cyclophosphamide

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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University Smilow Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: 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 Names: Herceptin; Drug: Paclitaxel; Administered at 80mg/m2 every week from week 1 to 12 (12 doses total).; Other Names: Taxol; Drug: 5-fluorouracil; Administered at 500 mg/m2 for every 3 weeks during weeks 13-24 (4 doses total).; Other Names: 5-FU; Drug: Epirubicin; Administered at 75mg/m2 every 3 weeks during weeks 13-24 (4 doses total).; Other Names: Ellence; Drug: Cyclophosphamide; Administered at 500mg/m2 for every 3 weeks during weeks 13-24 (4 doses total).; Other Names: Cytoxan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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 Outcome Measures

Outcome Measure	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	To assess clinical response according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, the number of patients are presented with a clinical response.	Up to 28 weeks
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.	Up to 28 weeks

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: Genentech, Inc.
• Investigators: Principal Investigator: Lajos Pusztai, MD, Yale University

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): August 1, 2018
• Study Completion (Actual): August 1, 2018

Study Registration Dates

• First Submitted: May 13, 2013
• First Submitted That Met QC Criteria: May 13, 2013
• First Posted (Estimate): May 17, 2013

Study Record Updates

• Last Update Posted (Actual): March 31, 2020
• Last Update Submitted That Met QC Criteria: March 18, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Cyclophosphamide; Paclitaxel; Trastuzumab; Fluorouracil; Epirubicin; Pertuzumab
• Other Study ID Numbers: 1305012136

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided