A Study of Trastuzumab Emtansine (T-DM1) Plus Pertuzumab/Pertuzumab Placebo Versus Trastuzumab [Herceptin] Plus a Taxane in Participants With Metastatic Breast Cancer (MARIANNE)
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: docetaxel; paclitaxel; pertuzumab; pertuzumab-placebo; trastuzumab [Herceptin]; trastuzumab emtansine
Intervention description: 75 mg/m2 or 100 mg/m2 intravenously every 3 weeks for a minimum of 6 cycles.; 80 mg/m2 intravenously weekly for a minimum of 18 weeks; 840 mg intravenously on day 1 of cycle 1 followed by 420 mg intravenously every 3 weeks in subsequent cycles; 840 mg intravenously on day 1 of cycle 1 followed by 420 mg intravenously every 3 weeks in subsequent cycles; trastuzumab [Herceptin] doses when administered with docetaxel: 8 mg/kg intravenously on cycle 1 followed by 6 mg/kg every 3 weeks in subsequent cycles or trastuzumab (Herceptin) doses when administered with paclitaxel: 4 mg/kg intravenously on day 1 of cycle 1 followed by 2 mg/kg weekly starting on day 8 of cycle 1.; 3.6 mg/kg intravenously every 3 weeks
Intervention MeSH terms: Paclitaxel; Maytansine; Docetaxel; Ado-Trastuzumab Emtansine; Trastuzumab; Pertuzumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 1095.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized, 3-arm, multicenter, phase III study will evaluate the efficacy and safety of
      trastuzumab emtansine (T-DM1) with pertuzumab or trastuzumab emtansine (T-DM1) with
      pertuzumab-placebo (blinded for pertuzumab), versus the combination of trastuzumab
      (Herceptin) plus taxane (docetaxel or paclitaxel) in participants with HER2-positive
      progressive or recurrent locally advanced or previously untreated metastatic breast cancer.
      Participants will be randomized to 1 of 3 treatment arms (Arms A, B or C). Arm A will be
      open-label, whereas Arms B and C will be blinded.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult participants >/=18 years of age

          -  HER2-positive breast cancer

          -  Histologically or cytologically confirmed adenocarcinoma of the breast with locally
             recurrent or metastatic disease, and be a candidate for chemotherapy. Participants
             with locally advanced disease must have recurrent or progressive disease, which must
             not be amenable to resection with curative intent.

          -  Participants must have measurable and/or non-measurable disease which must be
             evaluable per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1

          -  Adequate organ function as determined by laboratory results

        Exclusion Criteria:

          -  History of prior (or any) chemotherapy for metastatic breast cancer or recurrent
             locally advanced disease

          -  An interval of <6 months from the last dose of vinca-alkaloid or taxane cytotoxic
             chemotherapy until the time of metastatic diagnosis

          -  Hormone therapy <7 days prior to randomization

          -  Trastuzumab therapy and/or lapatinib (neo- or adjuvant setting) <21 days prior to
             randomization

          -  Prior trastuzumab emtansine or pertuzumab therapy