Overview

This trial is active, not recruiting.

Condition metastatic breast cancer
Treatments pertuzumab, placebo, trastuzumab, docetaxel
Phase phase 3
Targets HER, HER2
Sponsor Genentech
Collaborator Hoffmann-La Roche
Start date February 2008
End date May 2011
Trial size 808 participants
Trial identifier NCT00567190, TOC4129g, WO20698

Summary

This study is a Phase III, randomized, double-blind, placebo-controlled, multicenter international clinical trial. Patients who have human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) and have not received chemotherapy or biological therapy (including approved or investigational tyrosine kinase/HER inhibitors or vaccines) for their metastatic disease are eligible for study. Patients could have received one prior hormonal treatment for MBC. Patients may have received systemic breast cancer treatment in the neo-adjuvant or adjuvant setting, provided that the patient has experienced a disease-free interval (DFI) of ≥ 12 months from completion of adjuvant systemic treatment (excluding hormonal therapy) to metastatic diagnosis. Patients may have received trastuzumab and/or a taxane during the neo-adjuvant or adjuvant treatment.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Patients received pertuzumab 420 mg intravenously (IV) every 3 weeks (q3w) plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles.
pertuzumab Perjeta
Patients received a loading dose of 840 mg IV.
trastuzumab Herceptin
Patients received a loading dose of 8 mg/kg IV.
docetaxel Taxotere
At the investigator's discretion, the docetaxel dose could be increased to 100 mg/m^2 for patients who tolerated at least 1 cycle without significant toxicities.
(Placebo Comparator)
Patients received placebo IV q3w plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles.
placebo
trastuzumab Herceptin
Patients received a loading dose of 8 mg/kg IV.
docetaxel Taxotere
At the investigator's discretion, the docetaxel dose could be increased to 100 mg/m^2 for patients who tolerated at least 1 cycle without significant toxicities.

Primary Outcomes

Measure
Progression-free Survival (PFS) Determined by an Independent Review Facility
time frame: Baseline to data cut-off (up to 3 years, 3 months)

Secondary Outcomes

Measure
Overall Survival
time frame: Baseline to data cut-off (up to 3 years, 3 months)
Progression-free Survival (PFS) Determined by the Investigator
time frame: Baseline to data cut-off (up to 3 years, 3 months)
Objective Response
time frame: Baseline to data cut-off (up to 3 years, 3 months)
Duration of Objective Response
time frame: Baseline to data cut-off (up to 3 years, 3 months)
Time to Symptom Progression
time frame: Baseline to data cut-off (up to 3 years, 3 months)

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease, and candidate for chemotherapy. Patients with measurable and non-measurable disease are eligible (locally recurrent disease must not be amenable to resection with curative intent; patients with de novo Stage IV disease are eligible). - Human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). - Age ≥ 18 years. - Left ventricular ejection fraction (LVEF) ≥ 50% at baseline (within 42 days of randomization). - Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 0 or 1. - For women of childbearing potential, agreement to use an effective form of contraception and to continue its use for the duration of study treatment and for 6 months after the last dose of study treatment. - Signed, written informed consent obtained prior to any study procedure. Exclusion Criteria: - History of anti-cancer therapy for MBC (with the exception of one prior hormonal regimen for MBC). - History of approved or investigative tyrosine kinase/HER inhibitors for breast cancer in any treatment setting, except trastuzumab used in the neoadjuvant or adjuvant setting. - History of systemic breast cancer treatment in the neo-adjuvant or adjuvant setting with a disease-free interval from completion of the systemic treatment (excluding hormonal therapy) to metastatic diagnosis of < 12 months. - History of persistent Grade ≥ 2 hematologic toxicity resulting from previous adjuvant therapy. - Current peripheral neuropathy of National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 3.0, Grade ≥ 3 at randomization. - History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix or basal cell carcinoma. - Current clinical or radiographic evidence of central nervous system (CNS) metastases. - Computed tomography (CT) or magnetic resonance imaging (MRI) scan of the brain is mandatory in cases of clinical suspicion of brain metastases. - History of exposure to cumulative doses of anthracyclines. - Current uncontrolled hypertension or unstable angina. - History of congestive heart failure (CHF) of any New York Heart Association (NYHA) criteria, or serious cardiac arrhythmia requiring treatment. - History of myocardial infarction within 6 months of randomization. - History of LVEF decline to below 50% during or after prior trastuzumab neo-adjuvant or adjuvant therapy. - Current dyspnea at rest due to complications of advanced malignancy, or other diseases that require continuous oxygen therapy. - Inadequate organ function within 28 days prior to randomization. - Current severe, uncontrolled systemic disease. - Major surgical procedure or significant traumatic injury within 28 days prior to study treatment start or anticipation of the need for major surgery during the course of study treatment. - Pregnant or lactating women. - History of receiving any investigational treatment within 28 days of randomization. - Current known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). - Receipt of intravenous (IV) antibiotics for infection within 14 days of randomization. - Current chronic daily treatment with corticosteroids (excluding inhaled steroids). - Known hypersensitivity to any of the study drugs. - Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.

Additional Information

Official title A Phase III, Randomized, Double-blind, Placebo-controlled Clinical Trial to Evaluate the Efficacy and Safety of Pertuzumab + Trastuzumab + Docetaxel vs. Placebo + Trastuzumab + Docetaxel in Previously Untreated HER2-positive Metastatic Breast Cancer
Trial information was received from ClinicalTrials.gov and was last updated in January 2014.
Information provided to ClinicalTrials.gov by Genentech.