Clinical trial · Interventional
A Study of Vemurafenib (RO5185426) in Comparison With Dacarbazine in Previously Untreated Patients With Metastatic Melanoma (BRIM 3)
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
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Malignant Melanoma | Melanoma | ALIAS | 0.90 |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Dacarbazine | Drug | Dacarbazine | ALIAS |
| Vemurafenib | Drug | Vemurafenib | ALIAS |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- Vemurafenib
- interventionNames
- Drug: Vemurafenib
- type
- ACTIVE_COMPARATOR
- label
- Dacarbazine
- interventionNames
- Drug: Dacarbazine
Primary outcomes (2)
- measure
- Overall Survival
- timeFrame
- 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).
- description
- An Overall survival event was defined as death due to any cause. The number of participants with overall survival events is reported.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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
References
Publications (8)
- DERIVEDAscierto PA, Ribas A, Larkin J, McArthur GA, Lewis KD, Hauschild A, Flaherty KT, McKenna E, Zhu Q, Mun Y, Dreno B. Impact of initial treatment and prognostic factors on postprogression survival in BRAF-mutated metastatic melanoma treated with dacarbazine or vemurafenib +/- cobimetinib: a pooled analysis of four clinical trials. J Transl Med. 2020 Aug 3;18(1):294. doi: 10.1186/s12967-020-02458-x. PMID 32746839
- DERIVEDChapman PB, Robert C, Larkin J, Haanen JB, Ribas A, Hogg D, Hamid O, Ascierto PA, Testori A, Lorigan PC, Dummer R, Sosman JA, Flaherty KT, Chang I, Coleman S, Caro I, Hauschild A, McArthur GA. Vemurafenib in patients with BRAFV600 mutation-positive metastatic melanoma: final overall survival results of the randomized BRIM-3 study. Ann Oncol. 2017 Oct 1;28(10):2581-2587. doi: 10.1093/annonc/mdx339. PMID 28961848
- DERIVEDYamazaki N, Kiyohara Y, Sugaya N, Uhara H. Phase I/II study of vemurafenib in patients with unresectable or recurrent melanoma with BRAF(V) (600) mutations. J Dermatol. 2015 Jul;42(7):661-6. doi: 10.1111/1346-8138.12873. Epub 2015 Apr 17. PMID 25884515
- DERIVEDFrederick DT, Salas Fragomeni RA, Schalck A, Ferreiro-Neira I, Hoff T, Cooper ZA, Haq R, Panka DJ, Kwong LN, Davies MA, Cusack JC, Flaherty KT, Fisher DE, Mier JW, Wargo JA, Sullivan RJ. Clinical profiling of BCL-2 family members in the setting of BRAF inhibition offers a rationale for targeting de novo resistance using BH3 mimetics. PLoS One. 2014 Jul 1;9(7):e101286. doi: 10.1371/journal.pone.0101286. eCollection 2014. PMID 24983357
- DERIVEDMcArthur GA, Chapman PB, Robert C, Larkin J, Haanen JB, Dummer R, Ribas A, Hogg D, Hamid O, Ascierto PA, Garbe C, Testori A, Maio M, Lorigan P, Lebbe C, Jouary T, Schadendorf D, O'Day SJ, Kirkwood JM, Eggermont AM, Dreno B, Sosman JA, Flaherty KT, Yin M, Caro I, Cheng S, Trunzer K, Hauschild A. Safety and efficacy of vemurafenib in BRAF(V600E) and BRAF(V600K) mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study. Lancet Oncol. 2014 Mar;15(3):323-32. doi: 10.1016/S1470-2045(14)70012-9. Epub 2014 Feb 7.