A Study of RO5185426 in Comparison With Dacarbazine in Previously Untreated Patients With Metastatic Melanoma (BRIM 3)
This randomized, open-label study will evaluate the efficacy, safety and tolerability of RO5185426 as compared to dacarbazine in previously untreated patients with metastatic melanoma. Patients will be randomized to receive either RO5185426 [RG7204; PLEXXIKON: PLX4032] 960 mg orally twice daily or dacarbazine 1000 mg/m2 intravenously every 3 weeks. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs. Patients in the dacarbazine arm may cross over to RO5185426 treatment.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||BRIM 3: A Randomized, Open-label, Controlled, Multicenter, Global Study on Progression-free and Overall Survival in Previously Untreated Patients With Unresectable Stage IIIC or Stage IV Melanoma With V600E BRAF Mutation Receiving RO5185426 or Dacarbazine|
- 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). ] [ Designated as safety issue: No ]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. ] [ Designated as safety issue: No ]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).
- Participants With a Best Overall Response (BOR) of Complete Response or Partial Response [ Time Frame: From randomization (initiated January 2010) until December 30, 2010 ] [ Designated as safety issue: No ]BOR was defined as a complete response (CR) or partial response (PR) confirmed per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Patients who never received study treatment and treated patients 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. ] [ Designated as safety issue: No ]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 patients 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. ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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. ] [ Designated as safety issue: No ]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). ] [ Designated as safety issue: No ]The pharmacokinetics of vemurafenib were assessed at the beginning of each 21-day cycle using pre-dose and 2-4 hours post-dose sampling.
|Study Start Date:||January 2010|
|Estimated Study Completion Date:||June 2014|
|Primary Completion Date:||December 2010 (Final data collection date for primary outcome measure)|
960 mg orally twice daily
|Active Comparator: B||
1000 mg/m2 iv every 3 weeks
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|Study Director:||Clinical Trials||Hoffmann-La Roche|