A Study Of PF-05280014 [Trastuzumab-Pfizer] Or Herceptin® [Trastuzumab-EU] Plus Paclitaxel In HER2 Positive First Line Metastatic Breast Cancer Treatment (REFLECTIONS B327-02)
Condition: Metastatic Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: PF-05280014; Paclitaxel; Herceptin®; Paclitaxel
Intervention description: 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.; 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.; 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.; 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.
Intervention MeSH terms: Paclitaxel; Albumin-Bound Paclitaxel; Trastuzumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 707.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Phase 3; trastuzumab; Breast Neoplasms

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.
    

Eligibility criteria:

        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) and within 1 year before randomization.

          -  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.