A Study of Trastuzumab Emtansine (T-DM1) Plus Pertuzumab/Pertuzumab Placebo Versus Trastuzumab [Herceptin] Plus a Taxane in Participants With Metastatic Breast Cancer (MARIANNE)

Roche

Status and phase: Completed; Phase 3

Conditions: Breast Cancer

Treatments: Drug: paclitaxel; Drug: pertuzumab; Drug: docetaxel; Drug: trastuzumab [Herceptin]; Drug: pertuzumab-placebo; Drug: trastuzumab emtansine

Study type: Interventional

Funder types: Industry

Identifiers

NCT01120184

2009-017905-13 (EudraCT Number)

BO22589

Details and patient eligibility

About

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.

Enrollment: 1,095 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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1,095 participants in 3 patient groups

Trastuzumab + Taxane (docetaxel or paclitaxel)

Experimental group

Treatment:

Drug: trastuzumab [Herceptin]

Drug: paclitaxel

Drug: docetaxel

Trastuzumab emtansine + pertuzumab

Experimental group

Treatment:

Drug: pertuzumab

Drug: trastuzumab emtansine

Trastuzumab emtansine + pertuzumab placebo

Experimental group

Treatment:

Drug: pertuzumab-placebo

Drug: trastuzumab emtansine