NCT01120184
A Study of Trastuzumab Emtansine (T-DM1) Plus Pertuzumab/Pertuzumab Placebo Versus Trastuzumab [Herceptin] Plus a Taxane in Participants With Metastatic Breast Cancer (MARIANNE)
PHASE3
COMPLETED
NCT01120184
INTERVENTIONAL
A Randomized, 3 Arm, Multicenter, Phase III Study to Evaluate the Efficacy and the Safety of T-DM1 Combined With Pertuzumab or T-DM1 Combined With Pertuzumab-Placebo (Blinded for Pertuzumab), Versus the Combination of Trastuzumab Plus Taxane, as First Line Treatment in HER2 Positive Progressive or Recurrent Locally Advanced or Metastatic Breast Cancer
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.
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
Breast Cancer
- TREATMENT
-
- Type: DRUG
- Name: docetaxel
- Description: 75 mg/m2 or 100 mg/m2 intravenously every 3 weeks for a minimum of 6 cycles.
- Arm Group Labels: Trastuzumab + Taxane (docetaxel or paclitaxel)
-
- Type: DRUG
- Name: paclitaxel
- Description: 80 mg/m2 intravenously weekly for a minimum of 18 weeks
- Arm Group Labels: Trastuzumab + Taxane (docetaxel or paclitaxel)
-
- Type: DRUG
- Name: pertuzumab
- Description: 840 mg intravenously on day 1 of cycle 1 followed by 420 mg intravenously every 3 weeks in subsequent cycles
- Arm Group Labels: Trastuzumab emtansine + pertuzumab
-
- Type: DRUG
- Name: pertuzumab-placebo
- Description: 840 mg intravenously on day 1 of cycle 1 followed by 420 mg intravenously every 3 weeks in subsequent cycles
- Arm Group Labels: Trastuzumab emtansine + pertuzumab placebo
-
- Type: DRUG
- Name: trastuzumab [Herceptin]
- Description: 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.
- Arm Group Labels: Trastuzumab + Taxane (docetaxel or paclitaxel)
-
- Type: DRUG
- Name: trastuzumab emtansine
- Description: 3.6 mg/kg intravenously every 3 weeks
- Arm Group Labels: Trastuzumab emtansine + pertuzumab, Trastuzumab emtansine + pertuzumab placebo
- Hoffmann-La Roche