Overview

This trial is active, not recruiting.

Condition metastatic breast cancer
Treatments pf-05280014, paclitaxel, herceptin®
Phase phase 3
Target HER2
Sponsor Pfizer
Start date February 2014
End date August 2016
Trial size 690 participants
Trial identifier NCT01989676, 2013-001352-34, B3271002, REFLECTIONS B327-02

Summary

The current study will compare the efficacy, safety, pharmacokinetics and immunogenicity of PF-05280014 in combination with paclitaxel versus trastuzumab sourced from the European Union (trastuzumab-EU) with paclitaxel in female patients with HER2-positive, metastatic breast cancer in the first-line treatment setting. The hypothesis to be tested in this study is that the efficacy (ORR) of PF-05280014 is similar to trastuzumab-EU.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
pf-05280014 Trastuzumab-Pfizer
Concentrate for solution for infusion, sterile vial 150 mg. Initial dose of 4 mg/kg over 90 minutes (depending on tolerability) IV infusion, then 2 mg/kg over 30 to 90 minutes (depending on tolerability) IV infusion until disease progression. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the PF-05280014 regimen may be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
paclitaxel
A nonaqueous solution intended for dilution with a suitable parenteral fluid prior to intravenous infusion. Paclitaxel is available in 30 mg (5 mL), 100 mg (16.7 mL), and 300 mg (50 mL) multidose vials. Each mL of sterile nonpyrogenic solution contains 6 mg paclitaxel. The starting dose of paclitaxel will be 80 mg/m^2 by IV infusion over 60 minutes (duration of infusion may be modified according to local standard of care, if applicable). Provision is made for dose reduction to 70 mg/m^2 and then 60 mg/m^2 as needed. In the absence of disease progression in the judgment of the investigator or prohibitive toxicity, patients will receive treatment with paclitaxel for at least 6 cycles or until maximal benefit of response is obtained, in the judgment of the investigator.
(Active Comparator)
herceptin® Trastuzumab (EU)
Concentrate for solution for infusion, sterile vial 150 mg. Initial dose of 4 mg/kg over 90 minutes (depending on tolerability) IV infusion, then 2 mg/kg over 30 to 90 minutes (depending on tolerability) IV infusion weekly until disease progression. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the Herceptin® regimen may be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
paclitaxel
A nonaqueous solution intended for dilution with a suitable parenteral fluid prior to intravenous infusion. Paclitaxel is available in 30 mg (5 mL), 100 mg (16.7 mL), and 300 mg (50 mL) multidose vials. Each mL of sterile nonpyrogenic solution contains 6 mg paclitaxel. The starting dose of paclitaxel will be 80 mg/m^2 by IV infusion over 60 minutes (duration of infusion may be modified according to local standard of care, if applicable). Provision is made for dose reduction to 70 mg/m^2 and then 60 mg/m^2 as needed. In the absence of disease progression in the judgment of the investigator or prohibitive toxicity, patients will receive treatment with paclitaxel for at least 6 cycles or until maximal benefit of response is obtained, in the judgment of the investigator.

Primary Outcomes

Measure
Percentage of Participants With Objective Response Rate (ORR)
time frame: Week 25

Secondary Outcomes

Measure
Duration of Response (DOR)
time frame: up to 12 months
1-year Progression-Free Survival (PFS) Rate
time frame: up to 12 months
1-year Survival Rate
time frame: up to 12 months
Maximum Observed Plasma Concentration (Cmax)
time frame: up to 4 months
Minimum Observed Plasma Trough Concentration (Cmin)
time frame: up to 24 months
Incidence of ADA
time frame: up to 24 months

Eligibility Criteria

Female participants at least 18 years old.

Inclusion Criteria: - Histologically confirmed diagnosis of breast cancer. - Presence of metastatic disease. - 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 (except endocrine therapy). - 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.

Additional Information

Official title A Phase 3 Randomized, Double-Blind Study Of PFf-05280014 Plus Paclitaxel Versus Trastuzumab Plus Paclitaxel For The First-Line Treatment Of Patients With HER2-Positive Metastatic Breast Cancer
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Pfizer.