A Study Of PF-05280014 Or Trastuzumab Plus Taxotere® And Carboplatin In HER2 Positive Breast Cancer In The Neoadjuvant Setting (REFLECTIONS B327-04)
Condition: Early Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: PF-05280014; Taxotere®; Paraplatin®; Trastuzumab-EU; Taxotere®; Paraplatin®
Intervention description: Concentrate for solution for infusion, sterile vial 150 mg, Day 1 Cycle 1 will be a loading dose of 8 mg/kg infused over 90 minutes. Subsequent infusions will follow every 3 weeks (i.e., cycled every 21 days) with a dose of 6 mg/kg administered over 30 to 90 minutes depending on tolerability, maximum of 6 cycles.; Injection concentrate single-dose vials containing 20 mg (0.5 mL) or 80 mg (2 mL), each mL contains 40 mg docetaxel (anhydrous) and 1040 mg polysorbate 80, The starting dose of Taxotere® (docetaxel) will be 75 mg/m2 administered intravenously over 60 minutes every three weeks on Day 1 of each cycle (i.e., every 21 days), maximum 6 cycles.; Lyophilized powder, single-dose vials containing 50 mg, 150 mg, and 450 mg of Carboplatin for administration by intravenous infusion (each vial contains equal parts by weight of Carboplatin and mannitol), starting dose 6 AUC, over 15 minutes or longer every three weeks on Day 1 of each cycle (i.e., every 21 days), maximum 6 cycles.; Concentrate for solution for infusion, sterile vial 150 mg, Day 1 Cycle 1 will be a loading dose of 8 mg/kg infused over 90 minutes. Subsequent infusions will follow every 3 weeks (i.e., cycled every 21 days) with a dose of 6 mg/kg administered over 30 to 90 minutes depending on tolerability, maximum 6 cycles.; Injection concentrate single-dose vials containing 20 mg (0.5 mL) or 80 mg (2 mL), each mL contains 40 mg docetaxel (anhydrous) and 1040 mg polysorbate 80, The starting dose of Taxotere® (docetaxel) will be 75 mg/m2 administered intravenously over 60 minutes every three weeks on Day 1 of each cycle (i.e., every 21 days), maximum 6 cycles.; Lyophilized powder, single-dose vials containing 50 mg, 150 mg, and 450 mg of Carboplatin for administration by intravenous infusion (each vial contains equal parts by weight of Carboplatin and mannitol), starting dose 6 AUC, over 15 minutes or longer every three weeks on Day 1 of each cycle (i.e., every 21 days), maximum 6 cycles.
Intervention MeSH terms: Carboplatin; Docetaxel; 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: 226.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Biosimilars; Non-inferiority; Neoadjuvant Setting; Early Breast Cancer; PK; Phase 3; Trastuzumab; Herceptin; HER2 Positive

Summary:

      The current study will compare PK, efficacy, safety, and immunogenicity of PF-05280014
      (Trastuzumab-Pfizer) in combination with Taxotere® and Carboplatin (Paraplatin) versus
      Herceptin® (Trastuzumab-EU) approved in the EU in combination with Taxotere® and Carboplatin
      (Paraplatin) in patients with operable HER2 positive, breast cancer in the neoadjuvant
      setting. The hypothesis to be tested in this study is the percentage of patients with steady
      state Cycle 5 Ctrough (Cycle 6 pre-dose) >20 µg/mL of trastuzumab-Pfizer is similar to
      EU-approved trastuzumab, using a margin of -12.5%.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed HER2 overexpressing invasive breast cancer.

          -  Plan for definitive surgical resection of breast tumor (i.e., lumpectomy or
             mastectomy, and sentinel node (SN) biopsy or axillary lymph node dissection (ALND).

          -  Plan for neoadjuvant chemotherapy.

          -  Measurable disease in the breast after diagnostic biopsy, defined as longest diameter
             ≥ 2.0 cm.

        Exclusion Criteria:

          -  Bilateral breast cancer.

          -  Inflammatory breast cancer.

          -  Presence of known distant metastases.

          -  Received prior treatment, including chemotherapy, endocrine therapy, biologic therapy,
             radiation or surgery with the exception of diagnostic biopsy for primary breast
             cancer.