A Study to Evaluate the Efficacy and Safety of Trastuzumab Emtansine Versus the Combination of Trastuzumab Plus Docetaxel in Patients With HER2-positive Breast Cancer
Condition: Metastatic Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Trastuzumab; Trastuzumab Emtansine; Docetaxel
Intervention description: For the first three-week cycle, trastuzumab was administered IV at 8 mg/kg. For subsequent cycles, trastuzumab was administered IV at 6 mg/kg Q3W.; Trastuzumab emtansine 3.6 milligrams/kilogram (mg/kg) was administered intravenously (IV) over 30-90 minutes Q3W.; Docetaxel was administered IV at either 75 milligrams/square meter (mg/m^2) or 100 mg/m^2 Q3W.
Intervention MeSH terms: Docetaxel; Trastuzumab; Maytansine; Ado-Trastuzumab Emtansine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 49.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a Phase III, randomized, multicenter, multinational, two-arm, open-label clinical
      trial to investigate a first-line treatment of participants with human epidermal growth
      factor receptor-2 (HER2)-positive metastatic breast cancer. The study will enroll patients
      with HER2-positive, unresectable, locally advanced breast cancer (BC) if they have recurrent
      disease or progressive disease (PD) despite primary multi-modality therapy, and/or metastatic
      BC if they have not received prior chemotherapy for their metastatic disease. Eligible
      participants at up to approximately 40 sites in the Asia-Pacific region will be randomized in
      a 2:1 ratio to receive trastuzumab emtansine (Arm A) or trastuzumab plus docetaxel (Arm B).
      All study drugs will be administered at in-clinic visits occurring every three weeks during
      the treatment phase. Trastuzumab plus docetaxel was chosen as the comparator in the control
      group (Arm B), as it represents a common first-line treatment option used in this patient
      population in China and other Asia-Pacific countries.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age >/= 18 years

          -  HER2-positive disease, as defined by an immunohistochemistry test score of 3+ and/or
             in situ hybridization positivity, prospectively confirmed by a Sponsor-designated
             central laboratory prior to enrollment

          -  Histologically or cytologically confirmed adenocarcinoma of the breast with locally
             recurrent or metastatic disease appropriate for chemotherapy

          -  Patients must have measurable and/or non-measurable disease that is evaluable per the
             Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

          -  Adequate organ function

          -  For women of childbearing potential and men with partners of childbearing potential,
             agreement by the patient and/or partner to use two adequate non-hormonal forms of
             contraception during treatment and for at least 6 months after the last dose of study
             drug

        Exclusion Criteria:

          -  Pregnancy or lactation

          -  Current severe, uncontrolled systemic disease (e.g., clinically significant
             cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; bone
             fractures, except bone fractures because of disease under study)

          -  Currently known active infection with HIV, hepatitis B virus (HBV), or hepatitis C
             virus (HCV)

          -  Major surgical procedure or significant traumatic injury within approximately 28 days
             prior to randomization or anticipation of the need for major surgery during the course
             of study treatment

          -  Current peripheral neuropathy Grade >/= 2 per National Cancer Institute Common
             Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE, v4.0)

          -  History of systemic anti-cancer therapy after the diagnosis of metastatic breast
             cancer (MBC) or for recurrent locally advanced disease, with the exception of prior
             hormonal regimens for recurrent locally advanced disease or MBC

          -  An interval of < 12 months after the last dose of vinca alkaloid or taxane
             chemotherapy (i.e., for treatment of early stage, non-metastatic disease)

          -  Hormonal therapy < 7 days prior to randomization

          -  Trastuzumab < 21 days prior to randomization

          -  Lapatinib </= 14 days prior to randomization

          -  Prior trastuzumab emtansine therapy

          -  Treatment with any other anti-cancer therapy/investigational drug (not defined above)
             within 21 days prior to randomization

          -  History of other malignancy within the last 5 years, except for appropriately treated
             carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer,
             or other malignancies with an expected curative outcome

          -  Current chronic daily treatment with corticosteroids (dose > 10 mg/day
             methylprednisone equivalent)

          -  History of intolerance (including Grade 3 or 4 infusion reaction) or hypersensitivity
             to trastuzumab, murine proteins, docetaxel or paclitaxel

          -  Known hypersensitivity any of the study drugs, including excipients, or any drugs
             formulated in polysorbate 80