Working... Menu

A Study of Vemurafenib (RO5185426) in Comparison With Dacarbazine in Previously Untreated Patients With Metastatic Melanoma (BRIM 3)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01006980
Recruitment Status : Completed
First Posted : November 3, 2009
Results First Posted : November 16, 2011
Last Update Posted : September 28, 2016
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
This randomized, open-label study evaluated the efficacy, safety and tolerability of vemurafenib (RO5185426) as compared to dacarbazine in previously untreated patients with metastatic melanoma. Patients were randomized to receive either vemurafenib 960 mg orally twice daily or dacarbazine 1000 mg/m2 intravenously every 3 weeks. Study treatment was continued until disease progression or unacceptable toxicity occurred. The data and safety monitoring board recommended that patients in the dacarbazine group be allowed to cross over to receive vemurafenib, and the protocol was amended accordingly on January 14, 2011, as both overall survival and progression-free survival endpoints had met the prespecified criteria for statistical significance in favor of vemurafenib.

Condition or disease Intervention/treatment Phase
Malignant Melanoma Drug: Vemurafenib Drug: Dacarbazine Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 675 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: BRIM 3: A Randomized, Open-Label, Controlled, Multicenter, Phase III Study in Previously Untreated Patients With Unresectable Stage IIIC or Stage IV Melanoma With V600E BRAF Mutation Receiving Vemurafenib (RO5185426) or Dacarbazine
Study Start Date : January 2010
Actual Primary Completion Date : December 2010
Actual Study Completion Date : July 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: Vemurafenib Drug: Vemurafenib
960 mg (as 240 mg tables) orally twice daily
Other Names:
  • Zelboraf®
  • RO5185426

Active Comparator: Dacarbazine Drug: Dacarbazine
1000 mg/m2 intravenously every 3 weeks

Primary Outcome Measures :
  1. Overall Survival [ Time Frame: From randomization (initiated January 2010) to December 30 2010. Median follow-up time in the vemurafenib group was 3.75 months (range 0.3 to 10.8) and in the dacarbazine group was 2.33 months (range <0.1 to 10.3). ]
    An Overall survival event was defined as death due to any cause. The number of participants with overall survival events is reported.

  2. Progression-free Survival [ Time Frame: From randomization (initiated January 2010) to December 30 2010. ]
    A progression-free survival (PFS) event was defined as disease progression or death due to any cause. Tumor response (progression) was assessed according to the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria using computed tomography (CT) scans or magnetic resonance imaging (MRI).

Secondary Outcome Measures :
  1. Participants With a Best Overall Response (BOR) of Complete Response or Partial Response [ Time Frame: From randomization (initiated January 2010) until December 30, 2010 ]
    BOR was defined as a complete response (CR) or partial response (PR) confirmed per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Participants who never received study treatment and treated participants without any post-baseline tumor assessments were considered as non-responders. CR: Disappearance of all target lesions, all non-target lesions and no new lesion. Any pathological lymph nodes must have had reduction in the short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion and no new lesion.

  2. Duration of Response [ Time Frame: From randomization (initiated in January 2010) until December 30, 2010. ]
    Duration of response was defined as the time between the date of the earliest qualifying response and the date of disease progression or death due to any cause. Duration of response was calculated only for participants who had a best overall response of Complete Response or Partial Response and was estimated using the Kaplan-Meier method.

  3. Time to Confirmed Response [ Time Frame: From randomization (initiated January 2010) until December 30, 2010. ]
    Time to response was defined as the time from randomization to confirmed response (complete response or partial response).

  4. Time to Treatment Failure [ Time Frame: approximately 3 years ]
    Treatment failure was defined as a secondary endpoint in the protocol, defined as death, disease progression or premature withdrawal of study treatment. This endpoint was not included in the Statistical analysis plan; therefore no analyses of time to treatment failure were performed.

  5. Number of Participants With Adverse Events (AEs) [ Time Frame: From randomization (initiated January 2010) until December 30, 2010. ]
    The intensity of AEs was graded according to the NCI Common Terminology Criteria for Adverse Events v 4.0 (CTCAE) on a five-point scale (Grade 1 to 5: Mild, Moderate, Severe, Life-threatening and Death). A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution, for example is life-threatening, requires hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or requires intervention to prevent one or other of the outcomes listed above.

  6. Pre and Post-dose Plasma Vemurafenib Concentration by Study Day [ Time Frame: Plasma samples were collected before the morning dose (troughs) and 2-4 hours after the morning dose at the beginning of each cycle (Days 1, 22, 43, 64, 106, 148 and 190). ]
    The pharmacokinetics of vemurafenib were assessed at the beginning of each 21-day cycle using pre-dose and 2-4 hours post-dose sampling.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • adults, >/=18 years of age
  • metastatic melanoma, stage IIIC or IV (AJCC)
  • treatment-naïve (no prior systemic anticancer therapy)
  • positive for BRAF V600E mutation
  • measurable disease by RECIST criteria
  • negative pregnancy test and, for fertile men and women, effective contraception during treatment and for 6 months after completion

Exclusion Criteria:

  • active central nervous system metastases
  • history of carcinomatous meningitis
  • severe cardiovascular disease within 6 months prior to study drug administration
  • previous malignancy within 5 years prior to study, except for basal or squamous cell carcinoma of the skin, melanoma in-situ, or carcinoma in-situ of the cervix

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01006980

  Hide Study Locations
Layout table for location information
United States, Alabama
Birmingham, Alabama, United States, 35243
United States, Arizona
Tucson, Arizona, United States, 85724
United States, California
Los Angeles, California, United States, 90095-1752
San Francisco, California, United States, 94117
Santa Monica, California, United States, 90404
United States, Colorado
Aurora, Colorado, United States, 80045
United States, Georgia
Atlanta, Georgia, United States, 30322
United States, Indiana
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
Boston, Massachusetts, United States, 02114
Boston, Massachusetts, United States, 02115
Boston, Massachusetts, United States, 02215
United States, Michigan
Detroit, Michigan, United States, 48201
United States, Missouri
St Louis, Missouri, United States, 63110
United States, New York
New York, New York, United States, 10016
New York, New York, United States, 10065
United States, North Carolina
Chapel Hill, North Carolina, United States, 27514
United States, Oregon
Portland, Oregon, United States, 97213
United States, Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Pittsburgh, Pennsylvania, United States, 15213-2584
United States, Tennessee
Nashville, Tennessee, United States, 37203
Nashville, Tennessee, United States, 37232
United States, Texas
Dallas, Texas, United States, 75246
United States, Utah
Salt Lake City, Utah, United States, 84112
United States, Washington
Seattle, Washington, United States, 98109
Brisbane, Australia, 4006
Frankston, Australia, 3199
Malvern, Australia, 3144
Melbourne, Australia, 3002
Melbourne, Australia, 3128
Nedlands, Australia, 6009
Newcastle, Australia, 2310
St Leonards, Australia, 2065
Sydney, Australia, 2060
Westmead, Australia, 2145
Woolloongabba, Australia, 4102
Canada, Alberta
Edmonton, Alberta, Canada, T5J 3N4
Canada, Manitoba
Winnipeg, Manitoba, Canada, R2H 2A6
Canada, Ontario
Hamilton, Ontario, Canada, L8V 5C2
Toronto, Ontario, Canada, M4N 3M5
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Montreal, Quebec, Canada, H3A 1A1
Montreal, Quebec, Canada, H3T 1E2
Quebec City, Quebec, Canada, G1R 2J6
Bordeaux, France, 33075
Lille, France, 59037
Marseille, France, 13005
Montpellier, France, 34298
Nantes, France, 44093
Nice, France, 06202
Paris, France, 75010
Pierre Benite, France, 69495
Rouen, France, 76031
Villejuif, France, 94805
Buxtehude, Germany, 21614
Dresden, Germany, 01307
Erfurt, Germany, 99089
Essen, Germany, 45122
Frankfurt, Germany, 60596
Hannover, Germany, 30449
Heidelberg, Germany, 69120
Jena, Germany, 07743
Kiel, Germany, 24105
Koeln, Germany, 50924
Leipzig, Germany, 04103
Mainz, Germany, 55131
Minden, Germany, 32429
Muenchen, Germany, 81377
Regensburg, Germany, 93053
Tuebingen, Germany, 72076
Wuerzburg, Germany, 80337
Jerusalem, Israel, 91200
Ramat Gan, Israel, 52621
Tel Aviv, Israel, 64239
Bari, Italy, 70124
Genova, Italy, 16132
Milano, Italy, 20133
Milano, Italy, 20141
Milano, Italy, 20162
Napoli, Italy, 80131
Roma, Italy, 00158
Siena, Italy, 53100
Amsterdam, Netherlands, 1066 CX
Amsterdam, Netherlands, 1081 HV
Groningen, Netherlands, 9713 GZ
New Zealand
Auckland, New Zealand
Dunedin, New Zealand, 9001
Hamilton, New Zealand, 2001
Palmerston North, New Zealand
Wellington, New Zealand, 6021
Linkoeping, Sweden, 58185
Lund, Sweden, 22185
Stockholm, Sweden, 17176
Umeå, Sweden
Uppsala, Sweden, 75185
Lausanne, Switzerland, 1011
Zürich, Switzerland, 8091
United Kingdom
Cambridge, United Kingdom, CB2 2QH
Edinburgh, United Kingdom, EH4 2XU
Glasgow, United Kingdom, G12 0YN
London, United Kingdom, E1 1BB
London, United Kingdom, NW3 2QG
London, United Kingdom, SE1 9RT
London, United Kingdom, SW3 3JJ
Manchester, United Kingdom, M20 4BX
Newcastle Upon Tyne, United Kingdom, NE7 7DN
Northwood, United Kingdom, HA6 2RN
Nottingham, United Kingdom, NG5 1PB
Oxford, United Kingdom, OX3 7LJ
Southampton, United Kingdom, SO16 6YD
Sutton, United Kingdom, SM2 5PT
Swansea, United Kingdom, SA2 8QA
Sponsors and Collaborators
Hoffmann-La Roche
Layout table for investigator information
Study Director: Clinical Trials Hoffmann-La Roche

Publications automatically indexed to this study by Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Hoffmann-La Roche Identifier: NCT01006980     History of Changes
Other Study ID Numbers: NO25026
First Posted: November 3, 2009    Key Record Dates
Results First Posted: November 16, 2011
Last Update Posted: September 28, 2016
Last Verified: December 2015

Additional relevant MeSH terms:
Layout table for MeSH terms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action