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

NCT01855828 | Completed Phase 2 Results DMC

• 1 other identifier: 1305012136
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Her2-Positive Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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 (3)

• Cardiac Safety

  Up to 1 year post surgery

• Count of Patients With Clinical Response

  Up to 28 weeks

• Residual Cancer Burden Score

  Up to 28 weeks

Study Arms (1)

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

Pertuzumab DRUG

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

Also known as: Perjeta

Chemo plus Pertuzumab,Trastuzumab

Trastuzumab 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).

Also known as: Herceptin

Chemo plus Pertuzumab,Trastuzumab

Paclitaxel DRUG

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

Also known as: Taxol

Chemo plus Pertuzumab,Trastuzumab

5-fluorouracil DRUG

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

Also known as: 5-FU

Chemo plus Pertuzumab,Trastuzumab

Epirubicin DRUG

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

Also known as: Ellence

Chemo plus Pertuzumab,Trastuzumab

Cyclophosphamide DRUG

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

Also known as: Cytoxan

Chemo plus Pertuzumab,Trastuzumab

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Yale University: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Yale University Smilow Cancer Hospital

New Haven, Connecticut, 06520, United States

Location

MeSH Terms

Interventions

pertuzumab; Trastuzumab; Paclitaxel; Fluorouracil; Epirubicin; Cyclophosphamide

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Lajos Pusztai, MD, DPhil
• Organization: Yale University

lajos.pusztai@yale.edu

203-737-6858

Study Officials

• Lajos Pusztai, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2013
• First Posted: May 17, 2013
• Study Start: September 1, 2013
• Primary Completion: August 1, 2018
• Study Completion: August 1, 2018
• Last Updated: March 31, 2020
• Results First Posted: March 31, 2020

Record last verified: 2020-03

Locations

US (1)