A Phase 3 Randomized, Double-blind Study of PF-05280014 Plus Paclitaxel Versus Trastuzumab Plus Paclitaxel for the First-line Treatment of Patients with Her2-positive Metastatic Breast Cancer

PHRR140421-000192

2013-CT0156

2013-CT0156

A Phase 3 Randomized, Double-blind Study of PF-05280014 Plus Paclitaxel Versus Trastuzumab Plus Paclitaxel for the First-line Treatment of Patients with Her2-positive Metastatic Breast Cancer

This is an international, double-blind, randomized, Phase 3 clinical trial evaluating the efficacy, safety, PK and immunogenicity of Trastuzumab-Pfizer in combination with paclitaxel versus trastuzumab-EU with paclitaxel in patients with HER2-positive, metastatic breast cancer in the first-line treatment setting. The primary endpoint is ORR, evaluating responses achieved by Week 25 and subsequently confirmed, in accordance with RECIST 1.1. Central radiology review will be the basis for analysis of the primary endpoint. Secondary endpoints include safety, DOR, 1-year PFS, 1-year survival rate, selected peak and trough drug concentrations, and immunogenicity.

Completed

Metastatic Breast Cancer

•Percentage of Participants With Objective Response Rate (ORR) [ Time Frame: Week 25 ] [ Designated as safety issue: No ] The percent of patients within each treatment group that achieved Complete Response (CR) or Partial Response (PR) by Week 25 of the study (window ± 14 days) and confirmed on a follow-up assessment, in accordance with the RECIST 1.1.

•Duration of Response (DOR) [ Time Frame: up to 12 months ] [ Designated as safety issue: No ] The percent of patients The time from date of the first documentation of objective tumor response to the first documentation of PD or to death due to any cause in the absence of documented PD. •1-year Progression-Free Survival (PFS) Rate [ Time Frame: up to 12 months ] [ Designated as safety issue: No ] The time from date of randomization to first progression of disease (PD) or death due to any cause in the absence of documented PD. •1-year Survival Rate [ Time Frame: up to 12 months ] [ Designated as safety issue: No ] Duration from enrollment to death. For participants who are alive, overall survival will be censored at the last contact. •Maximum Observed Plasma Concentration (Cmax) [ Time Frame: up to 4 months ] [ Designated as safety issue: No ] Peak PF-05280014 and trastuzumab-EU concentrations at selected cycles. •Minimum Observed Plasma Trough Concentration (Cmin) [ Time Frame: up to 24 months ] [ Designated as safety issue: No ] Trough PF-05280014 and trastuzumab-EU concentrations at selected cycles. •Incidence of ADA [ Time Frame: up to 24 months ] [ Designated as safety issue: Yes ] The percentage of patients with positive ADA and neutralizing antibodies will be summarized for each treatment arm.

Completed

• Argentina
• Brazil
• Chile
• Czech Republic
• Greece
• Hungary
• India
• Italy
• Japan
• Mexico
• Philippines
• Poland
• Portugal
• Romania
• Russia
• Serbia and Montenegro
• South Africa
• South Korea
• Spain
• Thailand
• Turkey
• Ukraine
• United States

Clinical Trial

Unspecified

2013-12-05

0000-00-00

32

Unspecified

Unspecified

01 Mar 2014

Inclusion Criteria: •Histologically confirmed diagnosis of breast cancer. •Presence of metastatic disease. •Prior documentation of HER2 gene amplification or overexpression. •Available tumor tissue for central review of HER2 status. •At least 1 measurable lesion as defined by RECIST 1.1. •Eastern Cooperative Oncology Group status of 0 to 2. •Left ventricular ejection fraction within institutional range of normal, measured by either two dimensional echocardiogram or multigated acquisition scan. Exclusion Criteria: •Relapse within 1 year of last dose of previous adjuvant (including neoadjuvant) treatment. •Prior systemic therapy for metastatic disease (except endocrine therapy). •Prior cumulative dose of doxorubicin of >400 mg/m2, epirubicin dose >800 mg/m^2, or the equivalent dose for other anthracyclines or derivatives (eg, 72 mg/m^2 of mitoxantrone). If the patient has received more than one anthracycline, then the cumulative dose must not exceed the equivalent of 400 mg/m^2 of doxorubicin. •Inflammatory breast cancer. •Active uncontrolled or symptomatic central nervous system metastases

Interventional

Experimental: PF-05280014

This is an international, double-blind, randomized, Phase 3 clinical trial evaluating the efficacy, safety, PK and immunogenicity of trastuzumab-Pfizer in combination with paclitaxel versus trastuzumab-EU with paclitaxel in patients with HER2-positive, metastatic breast cancer in the first-line treatment setting. The primary endpoint is ORR, evaluating responses achieved by Week 25 and subsequently confirmed, in accordance with RECIST 1.1. Central radiology review will be the basis for analysis of the primary endpoint. Secondary endpoints include safety, DOR, 1-year PFS, 1-year survival rate, selected peak and trough drug concentrations, and immunogenicity.

Randomized

Double Blind

Unspecified

Parallel

To compare the objective response rate (ORR) in patients with metastatic HER2-positiven breast cancer who receive trastuzumab-Pfizer to those who receive trastuzumab-EU in combination with paclitaxel.

Phase III