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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01120184
First received: April 28, 2010
Last updated: May 13, 2013
Last verified: May 2013
History of Changes
  Purpose

This randomized, 3-arm, multicentre, 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 patients with HER2-positive progressive or recurrent locally advanced or previously untreated metastatic breast cancer. Patients 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.


Condition Intervention Phase
Breast Cancer
 Drug: trastuzumab emtansine
Drug: pertuzumab
Drug: pertuzumab-placebo
Drug: trastuzumab [Herceptin]
Drug: docetaxel
Drug: paclitaxel
 Phase 3

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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Hoffmann-La Roche:

Primary Outcome 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 ] [ Designated as safety issue: No ]
  • Incidence of adverse events (AEs) [ Time Frame: Up to approximately 78 months after study start ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 1-year survival rate [ Time Frame: From baseline to 1 year ] [ Designated as safety issue: No ]
  • Overall Survival (OS) rate [ Time Frame: Up to approximately 78 months after study start ] [ Designated as safety issue: No ]
  • Time-to-Treatment Failure as assessed by IRF [ Time Frame: Up to approximately 48 months after study start ] [ Designated as safety issue: No ]
  • Overall or objective response rate [ Time Frame: Up to approximately 48 months after study start ] [ Designated as safety issue: No ]
  • Clinical benefit rate [ Time Frame: Up to approximately 48 months after study start ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: Up to approximately 48 months after study start ] [ Designated as safety issue: No ]
  • Overall Survival (OS) truncated at 2 years [ Time Frame: Up to approximately 48 months after study start ] [ Designated as safety issue: No ]

Enrollment: 1095
Study Start Date: July 2010
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Trastuzumab + Taxane (docetaxel or paclitaxel) 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.
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
Experimental: Trastuzumab emtansine + pertuzumab Drug: trastuzumab emtansine
3.6 mg/kg intravenously every 3 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
Experimental: Trastuzumab emtansine + pertuzumab placebo Drug: trastuzumab emtansine
3.6 mg/kg intravenously every 3 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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01120184

  Show 294 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Genentech
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided by Hoffmann-La Roche

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01120184     History of Changes
Other Study ID Numbers: BO22589
Study First Received: April 28, 2010
Last Updated: May 13, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Maytansine
Docetaxel
Trastuzumab
 Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 22, 2013