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

This study has been completed.
Information provided by (Responsible Party):
Hoffmann-La Roche Identifier:
First received: October 30, 2009
Last updated: August 19, 2016
Last verified: December 2015
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 Intervention Phase
Malignant Melanoma Drug: Vemurafenib Drug: Dacarbazine Phase 3

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • 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.

  • 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:
  • 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.

  • 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.

  • 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).

  • 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.

  • 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.

  • 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.

Enrollment: 675
Study Start Date: January 2010
Study Completion Date: July 2015
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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
  Contacts and Locations
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Please refer to this study by its identifier: NCT01006980

  Show 111 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

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

Responsible Party: Hoffmann-La Roche Identifier: NCT01006980     History of Changes
Other Study ID Numbers: NO25026
Study First Received: October 30, 2009
Results First Received: July 29, 2011
Last Updated: August 19, 2016

Additional relevant MeSH terms:
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas processed this record on September 20, 2017