Phase 3
N=675
A Study of Vemurafenib (RO5185426) in Comparison With Dacarbazine in Previously Untreated Patients With Metastatic Melanoma (BRIM 3)
Malignant Melanoma
Bottom Line
View on ClinicalTrials.gov: NCT01006980 ↗Enrolled (actual)
675
Serious AEs
36.6%
Results posted
Nov 2011
Primary outcome: Primary: Overall Survival — 43; 75; 293; 261 participants — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Vemurafenib (Drug); Dacarbazine (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Dec 2010
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Overall Survival |
43; 75; 293; 261 | <0.0001 sig |
| PRIMARY Progression-free Survival |
104; 182; 171; 92 | <.0001 sig |
| SECONDARY Participants With a Best Overall Response (BOR) of Complete Response or Partial Response |
106; 12; 113; 208 | — |
| SECONDARY Duration of Response |
5.49; NA | — |
| SECONDARY Time to Confirmed Response |
1.45; 2.72 | — |
| SECONDARY Time to Treatment Failure |
— | — |
| SECONDARY Number of Participants With Adverse Events (AEs) |
326; 253; 110; 45 | — |
| SECONDARY Pre and Post-dose Plasma Vemurafenib Concentration by Study Day |
0; 4.3; 53.0; 54.0; 54.4; 54.4 | — |
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.
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT01006980). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.