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

Brief Summary

Official Title: “A Study of Trastuzumab-DM1 Plus Pertuzumab Versus Trastuzumab [Herceptin] Plus a Taxane in Patients With Metastatic Breast Cancer”

This randomized, 3-arm, multicentre, phase III study will evaluate the efficacy and safety of trastuzumab emtansine (T-DM1) with pertuzumab or trastuzumab emtan sine (T-DM1) with pertuzumab-placebo (blinded for pertuzumab), versus the combin ation of trastuzumab (Herceptin) plus taxane (docetaxel or paclitaxel) in patien ts with HER2-positive progressive or recurrent locally advanced or previously un treated metastatic breast cancer. Patients will be randomized to 1 of 3 treatmen t arms (Arms A, B or C). Arm A will be open-label, whereas Arms B and C will be blinded.

  • Study Type: Interventional
  • Study Design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment
  • Study Primary Completion Date: March 2016

Interventions Used in this Clinical Trial

  • Drug: docetaxel
    • 75 mg/m2 or 100 mg/m2 intravenously every 3 weeks for a minimum of 6 cycles.
  • Drug: paclitaxel
    • 80 mg/m2 intravenously weekly for a minimum of 18 weeks
  • Drug: pertuzumab
    • 840 mg intravenously on day 1 of cycle 1 followed by 420 mg intravenously every 3 weeks in subsequent cycles
  • Drug: pertuzumab-placebo
    • 840 mg intravenously on day 1 of cycle 1 followed by 420 mg intravenously every 3 weeks in subsequent cycles
  • Drug: trastuzumab emtansine
    • 3.6 mg/kg intravenously every 3 weeks
  • Drug: trastuzumab [Herceptin]
    • 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.

Arms, Groups and Cohorts in this Clinical Trial

  • Experimental: Trastuzumab + Taxane (docetaxel or paclitaxel)
  • Experimental: Trastuzumab emtansine + pertuzumab
  • Experimental: Trastuzumab emtansine + pertuzumab placebo

Outcome Measures for this Clinical Trial

Primary Measures

  • Progression Free Survival (PFS) based on tumor assessments performed by an Independent Review Facility (IRF)
    • Time Frame: Up to approximately 48 months after study start
      Safety Issue?: No
  • Incidence of adverse events (AEs)
    • Time Frame: Up to approximately 78 months after study start
      Safety Issue?: No

Secondary Measures

  • 1-year survival rate
    • Time Frame: From baseline to 1 year
      Safety Issue?: No
  • Overall Survival (OS) rate
    • Time Frame: Up to approximately 78 months after study start
      Safety Issue?: No
  • Overall or objective response rate
    • Time Frame: Up to approximately 48 months after study start
      Safety Issue?: No
  • Duration of response
    • Time Frame: Up to approximately 48 months after study start
      Safety Issue?: No
  • Time-to-Treatment Failure as assessed by IRF
    • Time Frame: Up to approximately 48 months after study start
      Safety Issue?: No
  • Clinical benefit rate
    • Time Frame: Up to approximately 48 months after study start
      Safety Issue?: No
  • Overall Survival (OS) truncated at 2 years
    • Time Frame: Up to approximately 48 months after study start
      Safety Issue?: No

Criteria for Participation in this Clinical Trial

Inclusion Criteria

  • Adult patients >/=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. Patients with locally advanced disease must have recurrent or progressive disease, which must not be amenable to resection with curative intent.
  • Patients must have measurable and/or non-measurable disease which must be evaluable per RECIST 1.1
  • 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial: No

Clinical Trial Investigator Information

  • Lead Sponsor
    • Hoffmann-La Roche
  • Collaborator
    • Genentech, Inc.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Clinical Trials, Study Director, Hoffmann-La Roche

Source

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The URL of this page is:
http://clinicaltrialsfeeds.org/clinical-trials/show/NCT01120184