Study in Participants With Early-Stage or Locally Advanced Human Epidermal Growth Factor Receptor (HER) 2-Positive Breast Cancer to Evaluate Treatment With Trastuzumab Plus (+) Pertuzumab + Docetaxel Compared With Trastuzumab + Placebo + Docetaxel
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: FEC Chemotherapy; Surgery; Docetaxel; Pertuzumab; Placebo; Trastuzumab
Intervention description: Fluorouracil 500-600 milligrams per square meter (mg/m2), epirubicin 90-120 mg/m2, and cyclophosphamide 500-600 mg/m2 by intravenous (IV) infusion every 3 weeks for three cycles (Cycles 5-7). FEC chemotherapeutic agents will be administered following surgery on Day 1 of each specified cycle.; All participants who are eligible for surgery will undergo surgery and have their pathologic response evaluated.; Docetaxel IV infusion in 3-week cycles. Neoadjuvant treatment: 75 mg/m2 for Cycles 1-4.; Pertuzumab IV infusion in 3-week cycles. Prior to surgery (neoadjuvant treatment): 840 milligrams (mg) loading dose for Cycle 1, followed by 420 mg for Cycles 2-4. After surgery and 3 cycles of FEC chemotherapy (adjuvant treatment): 840 mg loading dose for Cycle 8, followed by 420 mg for Cycles 9-20); Placebo by IV infusion in 3-week cycles as neoadjuvant treatment (Cycles 1-4)and as adjuvant treatment (Cycles 8-20); Trastuzumab IV infusion in 3-week cycles. Neoadjuvant treatment: 8 milligrams per kilogram (mg/kg) loading dose for Cycle 1, followed by 6 mg/kg for Cycles 2-4. Adjuvant treatment: 8 mg/kg loading dose for Cycle 8, followed by 6 mg/kg for Cycles 9-20.
Intervention MeSH terms: Docetaxel; Trastuzumab; Pertuzumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 329.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is an Asia-Pacific regional, randomized, double-blind, multicenter trial designed to
      evaluate treatment with trastuzumab + pertuzumab + docetaxel compared with trastuzumab +
      placebo + docetaxel in chemotherapy-naïve participants with early-stage or locally advanced
      HER2-positive breast cancer. The anticipated treatment duration is approximately 17 months.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed invasive breast carcinoma with a primary tumor size of more
             than (>) 2 centimeters (cm) by standard local assessment technique

          -  Breast cancer stage at presentation: early-stage (T2-3, N0-1, M0) or locally advanced
             (T2-3, N2 or N3, M0; T4, any N, M0)

          -  HER2-positive breast cancer confirmed by a Sponsor-designated central laboratory and
             defined as 3+ score by immunohistochemistry in > 10 percent (%) of immunoreactive
             cells or HER2 gene amplification (ratio of HER2 gene signals to centromere 17 signals
             equal to or more than [>=] 2.0) by in situ hybridization

          -  Known hormone receptor status (estrogen receptor and/or progesterone receptor)

          -  Eastern Cooperative Oncology Group Performance Status equal to or less than (<=) 1

          -  Baseline left ventricular ejection fracture >= 55% measured by echocardiography
             (preferred) or multiple gated acquisition scan

          -  Negative serum pregnancy test

        Exclusion Criteria:

          -  Stage IV metastatic breast cancer

          -  Inflammatory breast cancer

          -  Previous anti-cancer therapy or radiotherapy for any malignancy

          -  History of other malignancy within 5 years prior to screening, except for
             appropriately-treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or
             Stage I uterine cancer

          -  Concurrent anti-cancer treatment in another investigational trial, including hormone
             therapy, bisphosphonate therapy, or immunotherapy

          -  Major surgical procedure unrelated to breast cancer within 4 weeks prior to
             randomization or from which the participant has not fully recovered

          -  Serious cardiac illness or medical condition

          -  Other concurrent serious diseases that may interfere with planned treatment, including
             severe pulmonary conditions/illness

          -  Any abnormalities in liver, kidney or hematologic function laboratory tests
             immediately prior to randomization

          -  Sensitivity to any of the study medications, any of the ingredients or excipients of
             these medications, or benzyl alcohol

          -  Pregnant or lactating