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
2 other identifiers
interventional
675
12 countries
111
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jan 2010
Longer than P75 for phase_3
111 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 30, 2009
CompletedFirst Posted
Study publicly available on registry
November 3, 2009
CompletedStudy Start
First participant enrolled
January 1, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2010
CompletedResults Posted
Study results publicly available
November 16, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2015
CompletedSeptember 28, 2016
December 1, 2015
11 months
October 30, 2009
July 29, 2011
August 19, 2016
Conditions
Outcome Measures
Primary Outcomes (2)
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).
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.
Secondary Outcomes (6)
Participants With a Best Overall Response (BOR) of Complete Response or Partial Response
From randomization (initiated January 2010) until December 30, 2010
Duration of Response
From randomization (initiated in January 2010) until December 30, 2010.
Time to Confirmed Response
From randomization (initiated January 2010) until December 30, 2010.
Time to Treatment Failure
approximately 3 years
Number of Participants With Adverse Events (AEs)
From randomization (initiated January 2010) until December 30, 2010.
- +1 more secondary outcomes
Study Arms (2)
Vemurafenib
EXPERIMENTALDacarbazine
ACTIVE COMPARATORInterventions
960 mg (as 240 mg tables) orally twice daily
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (111)
Unknown Facility
Birmingham, Alabama, 35243, United States
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Tucson, Arizona, 85724, United States
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Los Angeles, California, 90095-1752, United States
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San Francisco, California, 94117, United States
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Santa Monica, California, 90404, United States
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Aurora, Colorado, 80045, United States
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Atlanta, Georgia, 30322, United States
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Indianapolis, Indiana, 46202, United States
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Boston, Massachusetts, 02114, United States
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Boston, Massachusetts, 02115, United States
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Boston, Massachusetts, 02215, United States
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Detroit, Michigan, 48201, United States
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St Louis, Missouri, 63110, United States
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New York, New York, 10016, United States
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New York, New York, 10065, United States
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Chapel Hill, North Carolina, 27514, United States
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Portland, Oregon, 97213, United States
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Philadelphia, Pennsylvania, 19104, United States
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Pittsburgh, Pennsylvania, 15213-2584, United States
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Nashville, Tennessee, 37203, United States
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Nashville, Tennessee, 37232, United States
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Dallas, Texas, 75246, United States
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Salt Lake City, Utah, 84112, United States
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Seattle, Washington, 98109, United States
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Brisbane, 4006, Australia
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Frankston, 3199, Australia
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Malvern, 3144, Australia
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Melbourne, 3002, Australia
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Melbourne, 3128, Australia
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Nedlands, 6009, Australia
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Newcastle, 2310, Australia
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St Leonards, 2065, Australia
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Sydney, 2060, Australia
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Westmead, 2145, Australia
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Woolloongabba, 4102, Australia
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Edmonton, Alberta, T5J 3N4, Canada
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Winnipeg, Manitoba, R2H 2A6, Canada
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Hamilton, Ontario, L8V 5C2, Canada
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Toronto, Ontario, M4N 3M5, Canada
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Toronto, Ontario, M5G 2M9, Canada
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Montreal, Quebec, H3A 1A1, Canada
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Montreal, Quebec, H3T 1E2, Canada
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Québec, Quebec, G1R 2J6, Canada
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Bordeaux, 33075, France
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Lille, 59037, France
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Marseille, 13005, France
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Montpellier, 34298, France
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Nantes, 44093, France
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Nice, 06202, France
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Paris, 75010, France
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Pierre-Bénite, 69495, France
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Rouen, 76031, France
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Villejuif, 94805, France
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Buxtehude, 21614, Germany
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Cologne, 50924, Germany
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Dresden, 01307, Germany
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Erfurt, 99089, Germany
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Essen, 45122, Germany
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Frankfurt, 60596, Germany
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Hanover, 30449, Germany
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Heidelberg, 69120, Germany
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Jena, 07743, Germany
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Kiel, 24105, Germany
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Leipzig, 04103, Germany
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Mainz, 55131, Germany
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Minden, 32429, Germany
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München, 81377, Germany
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Regensburg, 93053, Germany
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Tübingen, 72076, Germany
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Würzburg, 80337, Germany
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Jerusalem, 91200, Israel
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Ramat Gan, 52621, Israel
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Tel Aviv, 64239, Israel
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Bari, 70124, Italy
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Genova, 16132, Italy
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Milan, 20133, Italy
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Milan, 20141, Italy
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Milan, 20162, Italy
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Napoli, 80131, Italy
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Roma, 00158, Italy
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Siena, 53100, Italy
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Amsterdam, 1066 CX, Netherlands
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Amsterdam, 1081 HV, Netherlands
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Groningen, 9713 GZ, Netherlands
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Auckland, New Zealand
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Dunedin, 9001, New Zealand
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Hamilton, 2001, New Zealand
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Palmerston North, New Zealand
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Wellington, 6021, New Zealand
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Linköping, 58185, Sweden
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Lund, 22185, Sweden
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Stockholm, 17176, Sweden
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Umeå, Sweden
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Uppsala, 75185, Sweden
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Lausanne, 1011, Switzerland
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Zurich, 8091, Switzerland
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Cambridge, CB2 2QH, United Kingdom
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Edinburgh, EH4 2XU, United Kingdom
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Glasgow, G12 0YN, United Kingdom
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London, E1 1BB, United Kingdom
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London, NW3 2QG, United Kingdom
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London, SE1 9RT, United Kingdom
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London, SW3 3JJ, United Kingdom
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Manchester, M20 4BX, United Kingdom
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Newcastle upon Tyne, NE7 7DN, United Kingdom
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Northwood, HA6 2RN, United Kingdom
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Nottingham, NG5 1PB, United Kingdom
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Oxford, OX3 7LJ, United Kingdom
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Southampton, SO16 6YD, United Kingdom
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Sutton, SM2 5PT, United Kingdom
Unknown Facility
Swansea, SA2 8QA, United Kingdom
Related Publications (8)
Ascierto 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: 32746839DERIVEDChapman 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: 28961848DERIVEDYamazaki 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: 25884515DERIVEDFrederick 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: 24983357DERIVEDMcArthur 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.
PMID: 24508103DERIVEDLacouture ME, Duvic M, Hauschild A, Prieto VG, Robert C, Schadendorf D, Kim CC, McCormack CJ, Myskowski PL, Spleiss O, Trunzer K, Su F, Nelson B, Nolop KB, Grippo JF, Lee RJ, Klimek MJ, Troy JL, Joe AK. Analysis of dermatologic events in vemurafenib-treated patients with melanoma. Oncologist. 2013;18(3):314-22. doi: 10.1634/theoncologist.2012-0333. Epub 2013 Mar 1.
PMID: 23457002DERIVEDSu F, Viros A, Milagre C, Trunzer K, Bollag G, Spleiss O, Reis-Filho JS, Kong X, Koya RC, Flaherty KT, Chapman PB, Kim MJ, Hayward R, Martin M, Yang H, Wang Q, Hilton H, Hang JS, Noe J, Lambros M, Geyer F, Dhomen N, Niculescu-Duvaz I, Zambon A, Niculescu-Duvaz D, Preece N, Robert L, Otte NJ, Mok S, Kee D, Ma Y, Zhang C, Habets G, Burton EA, Wong B, Nguyen H, Kockx M, Andries L, Lestini B, Nolop KB, Lee RJ, Joe AK, Troy JL, Gonzalez R, Hutson TE, Puzanov I, Chmielowski B, Springer CJ, McArthur GA, Sosman JA, Lo RS, Ribas A, Marais R. RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N Engl J Med. 2012 Jan 19;366(3):207-15. doi: 10.1056/NEJMoa1105358.
PMID: 22256804DERIVEDChapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, Dummer R, Garbe C, Testori A, Maio M, Hogg D, Lorigan P, Lebbe C, Jouary T, Schadendorf D, Ribas A, O'Day SJ, Sosman JA, Kirkwood JM, Eggermont AM, Dreno B, Nolop K, Li J, Nelson B, Hou J, Lee RJ, Flaherty KT, McArthur GA; BRIM-3 Study Group. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011 Jun 30;364(26):2507-16. doi: 10.1056/NEJMoa1103782. Epub 2011 Jun 5.
PMID: 21639808DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Communications
- Organization
- Hoffman-LaRoche
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 30, 2009
First Posted
November 3, 2009
Study Start
January 1, 2010
Primary Completion
December 1, 2010
Study Completion
July 1, 2015
Last Updated
September 28, 2016
Results First Posted
November 16, 2011
Record last verified: 2015-12