Skip to main content
OpenTrials
Completed

NCT Number: NCT01006980

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Malignant Melanoma Melanoma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Nerve Tissue Neuroectodermal Tumors Neuroendocrine Tumors Nevi and Melanomas Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Brisbane, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Vemurafenib

Drug

960 mg (as 240 mg tables) orally twice daily

Other names: Zelboraf®, RO5185426

Dacarbazine

Drug

1000 mg/m2 intravenously every 3 weeks

Primary outcomes

  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 outcomes

  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.

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study 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

Important dates

Study start
2010
Primary completion
2010
Study completion
2015
First posted
Nov 3, 2009
Registry last updated
Sep 28, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.