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

Malignant Melanoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01006980
• Other study ID #: NO25026
• Secondary ID: 2009-012293-12
• Status: Completed
• Phase: Phase 3
• First received: October 30, 2009
• Last updated: December 31, 2015
• Start date: January 2010
• Est. completion date: April 2015

Study information

• Verified date: December 2015
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 677
• Est. completion date: April 2015
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• adult patients, >/=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 CNS 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Malignant Melanoma
• Melanoma

Intervention

Drug:
• RO5185426
960 mg orally twice daily
• dacarbazine
1000 mg/m2 iv every 3 weeks

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Germany,  Israel,  Italy,  Netherlands,  New Zealand,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	An Overall survival event was defined as death due to any cause. The number of participants with overall survival events is reported.	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).	No
Primary	Progression-free Survival	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).	From randomization (initiated January 2010) to December 30 2010.	No
Secondary	Participants With a Best Overall Response (BOR) of Complete Response or Partial Response	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.	From randomization (initiated January 2010) until December 30, 2010	No
Secondary	Duration of Response	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.	From randomization (initiated in January 2010) until December 30, 2010.	No
Secondary	Time to Confirmed Response	Time to response was defined as the time from randomization to confirmed response (complete response or partial response).	From randomization (initiated January 2010) until December 30, 2010.	No
Secondary	Time to Treatment Failure	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.	approximately 3 years	No
Secondary	Number of Participants With Adverse Events (AEs)	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.	From randomization (initiated January 2010) until December 30, 2010.	No
Secondary	Pre and Post-dose Plasma Vemurafenib Concentration by Study Day	The pharmacokinetics of vemurafenib were assessed at the beginning of each 21-day cycle using pre-dose and 2-4 hours post-dose sampling.	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).	No