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

NCT ID: NCT01006980

Last Updated: 2016-09-28

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

675 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-01-31

Study Completion Date

2015-07-31

Brief Summary

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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.

Detailed Description

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Conditions

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Malignant Melanoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Vemurafenib

Group Type EXPERIMENTAL

Vemurafenib

Intervention Type DRUG

960 mg (as 240 mg tables) orally twice daily

Dacarbazine

Group Type ACTIVE_COMPARATOR

Dacarbazine

Intervention Type DRUG

1000 mg/m2 intravenously every 3 weeks

Interventions

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Vemurafenib

960 mg (as 240 mg tables) orally twice daily

Intervention Type DRUG

Dacarbazine

1000 mg/m2 intravenously every 3 weeks

Intervention Type DRUG

Other Intervention Names

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Zelboraf® RO5185426

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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Birmingham, Alabama, United States

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Tucson, Arizona, United States

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Los Angeles, California, United States

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San Francisco, California, United States

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Santa Monica, California, United States

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Aurora, Colorado, United States

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Atlanta, Georgia, United States

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Indianapolis, Indiana, United States

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Boston, Massachusetts, United States

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Boston, Massachusetts, United States

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Boston, Massachusetts, United States

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Detroit, Michigan, United States

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St Louis, Missouri, United States

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New York, New York, United States

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New York, New York, United States

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Chapel Hill, North Carolina, United States

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Portland, Oregon, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Nashville, Tennessee, United States

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Nashville, Tennessee, United States

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Dallas, Texas, United States

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Salt Lake City, Utah, United States

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Seattle, Washington, United States

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Brisbane, , Australia

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Frankston, , Australia

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Malvern, , Australia

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Melbourne, , Australia

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Melbourne, , Australia

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Nedlands, , Australia

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Newcastle, , Australia

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St Leonards, , Australia

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Sydney, , Australia

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Westmead, , Australia

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Woolloongabba, , Australia

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Edmonton, Alberta, Canada

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Winnipeg, Manitoba, Canada

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Hamilton, Ontario, Canada

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Toronto, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Bordeaux, , France

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Lille, , France

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Marseille, , France

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Montpellier, , France

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Nantes, , France

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Nice, , France

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Paris, , France

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Pierre-Bénite, , France

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Rouen, , France

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Villejuif, , France

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Buxtehude, , Germany

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Cologne, , Germany

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Dresden, , Germany

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Erfurt, , Germany

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Essen, , Germany

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Frankfurt, , Germany

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Hanover, , Germany

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Heidelberg, , Germany

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Jena, , Germany

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Kiel, , Germany

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Leipzig, , Germany

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Mainz, , Germany

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Minden, , Germany

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München, , Germany

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Regensburg, , Germany

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Tübingen, , Germany

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Würzburg, , Germany

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Jerusalem, , Israel

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Ramat Gan, , Israel

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Tel Aviv, , Israel

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Bari, , Italy

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Genova, , Italy

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Milan, , Italy

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Milan, , Italy

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Milan, , Italy

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Napoli, , Italy

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Roma, , Italy

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Siena, , Italy

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Amsterdam, , Netherlands

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Amsterdam, , Netherlands

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Groningen, , Netherlands

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Auckland, , New Zealand

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Dunedin, , New Zealand

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Hamilton, , New Zealand

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Palmerston North, , New Zealand

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Wellington, , New Zealand

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Linköping, , Sweden

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Lund, , Sweden

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Stockholm, , Sweden

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Umeå, , Sweden

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Uppsala, , Sweden

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Lausanne, , Switzerland

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Zurich, , Switzerland

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Cambridge, , United Kingdom

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Edinburgh, , United Kingdom

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Glasgow, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

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Newcastle upon Tyne, , United Kingdom

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Northwood, , United Kingdom

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Nottingham, , United Kingdom

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Oxford, , United Kingdom

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Southampton, , United Kingdom

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Sutton, , United Kingdom

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Swansea, , United Kingdom

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Countries

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

References

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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.

Reference Type DERIVED
PMID: 32746839 (View on PubMed)

Chapman 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.

Reference Type DERIVED
PMID: 28961848 (View on PubMed)

Yamazaki 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.

Reference Type DERIVED
PMID: 25884515 (View on PubMed)

Frederick 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.

Reference Type DERIVED
PMID: 24983357 (View on PubMed)

McArthur 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.

Reference Type DERIVED
PMID: 24508103 (View on PubMed)

Lacouture 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.

Reference Type DERIVED
PMID: 23457002 (View on PubMed)

Su 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.

Reference Type DERIVED
PMID: 22256804 (View on PubMed)

Chapman 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.

Reference Type DERIVED
PMID: 21639808 (View on PubMed)

Other Identifiers

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2009-012293-12

Identifier Type: -

Identifier Source: secondary_id

NO25026

Identifier Type: -

Identifier Source: org_study_id

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