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

Sponsor:	Hoffmann-La Roche
Collaborator:	Genentech
Information provided by:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT01120184

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:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Paclitaxel Docetaxel Trastuzumab

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 ]

Estimated Enrollment:	1092
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

Contacts

Contact: Please reference Study ID Number: BO22589

888-662-6728 (U.S. Only)

genentechclinicaltrials@druginfo.com

Show 292 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):

Scott AM, Wolchok JD, Old LJ. Antibody therapy of cancer. Nat Rev Cancer. 2012 Mar 22;12(4):278-87. doi: 10.1038/nrc3236.

Responsible Party:	Disclosures Group, Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT01120184 History of Changes
Other Study ID Numbers:	BO22589
Study First Received:	April 28, 2010
Last Updated:	March 16, 2012
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
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 23, 2012