A Study to Compare Subcutaneous (SC) Versus Intravenous (IV) Administration of Herceptin (Trastuzumab) in Women With Human Epidermal Growth Factor Receptor (HER) 2-Positive Early Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: 5-Fluorouracil; Cyclophosphamide; Docetaxel; Epirubicin; Herceptin IV [trastuzumab]; Herceptin SC [trastuzumab]
Intervention description: Participants will receive 5-fluorouracil, 500 milligrams per meter-squared (mg/m^2) via IV bolus or infusion, on Day 1 of every 21-day cycle during Cycles 5 to 8.; Participants will receive cyclophosphamide, 500 mg/m^2 via IV bolus, on Day 1 of every 21-day cycle during Cycles 5 to 8.; Participants will receive docetaxel, 75 mg/m^2 via IV infusion on Day 1 of every 21-day cycle during Cycles 1 to 4.; Participants will receive epirubicin, 75 mg/m^2 via IV bolus or infusion, on Day 1 of every 21-day cycle during Cycles 5 to 8.; Herceptin will be administered as 8 mg/kg (loading dose during Cycle 1) and 6 mg/kg (subsequent cycles) via IV infusion on Day 1 of each 21-day cycle for a total of 18 cycles.; Herceptin will be administered as fixed dose 600 mg SC on Day 1 of each 21-day cycle for a total of 18 cycles.
Intervention MeSH terms: Cyclophosphamide; Docetaxel; Fluorouracil; Trastuzumab; Epirubicin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 596.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      In this open-label multicenter trial, participants with operable or locally advanced breast
      cancer will be randomized to pre-operative treatment with 8 cycles of chemotherapy (4 cycles
      of docetaxel followed by 4 cycles of 5-fluorouracil, epirubicin, and cyclophosphamide)
      concurrent with either SC Herceptin or IV Herceptin. After surgery, participants will receive
      a further 10 cycles of SC or IV Herceptin as per randomization to complete 1 year of
      treatment. All cycles will be 21 days in length. After the end of study treatment,
      participants will be followed for safety and efficacy for up to 5 years or until disease
      recurrence, whichever is earlier.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult women greater than or equal to (≥) 18 years of age

          -  Non-metastatic primary invasive adenocarcinoma of the breast clinical stage I to IIIC,
             including inflammatory and multicentric/multifocal breast cancer, with tumor size ≥1
             centimeter (cm) by ultrasound or ≥2 cm by palpation, centrally confirmed HER2-positive
             (immunohistochemical score [IHC] 3+ or in situ hybridization [ISH]-positive)

          -  At least 1 measurable lesion in breast or lymph nodes (≥1 cm by ultrasound or ≥2 cm by
             palpation), except for inflammatory carcinoma (T4d)

          -  Baseline left ventricular ejection fraction (LVEF) ≥55%

          -  Eastern Cooperative Oncology Group (ECOG) status of 0 or 1

          -  Adequate organ function at Baseline

        Exclusion Criteria:

          -  History of any prior (ipsilateral and/or contralateral) invasive breast carcinoma

          -  Past or current history of malignant neoplasms, except for curatively treated basal
             and squamous cell carcinoma of the skin and in situ carcinoma of the cervix

          -  Metastatic disease

          -  Any prior therapy with anthracyclines

          -  Prior anti-HER2 therapy or biologic or immunotherapy

          -  Serious cardiac illness

          -  Pregnant or lactating women