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Malignant MelanomaPhase 3NCT01006980

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

A Phase 3 study testing Vemurafenib and Dacarbazine in people with Malignant Melanoma, run by Hoffmann-La Roche at 111 sites in 12 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Malignant Melanoma
What is being tested?
Vemurafenib and Dacarbazine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
675 participants
Where
111 sitesin 12 countries
Study dates
Jan 2010to Jul 2015
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

111 sites in 12 countries.

111 sites in 12 countries

United States24 sites

  • Study site

    Atlanta, Georgia, 30322

  • Study site

    Aurora, Colorado, 80045

  • Study site

    Birmingham, Alabama, 35243

  • Study site

    Boston, Massachusetts, 02114

  • Study site

    Boston, Massachusetts, 02115

  • Study site

    Boston, Massachusetts, 02215

  • Study site

    Chapel Hill, North Carolina, 27514

  • Study site

    Dallas, Texas, 75246

  • Study site

    Detroit, Michigan, 48201

  • Study site

    Indianapolis, Indiana, 46202

  • Study site

    Los Angeles, California, 90095-1752

  • Study site

    Nashville, Tennessee, 37203

  • Study site

    Nashville, Tennessee, 37232

  • Study site

    New York, New York, 10016

  • Study site

    New York, New York, 10065

  • Study site

    Philadelphia, Pennsylvania, 19104

  • Study site

    Pittsburgh, Pennsylvania, 15213-2584

  • Study site

    Portland, Oregon, 97213

  • Study site

    Salt Lake City, Utah, 84112

  • Study site

    San Francisco, California, 94117

  • Study site

    Santa Monica, California, 90404

  • Study site

    Seattle, Washington, 98109

  • Study site

    St Louis, Missouri, 63110

  • Study site

    Tucson, Arizona, 85724

Other trials in United States

Germany17 sites

  • Study site

    Buxtehude, 21614

  • Study site

    Cologne, 50924

  • Study site

    Dresden, 01307

  • Study site

    Erfurt, 99089

  • Study site

    Essen, 45122

  • Study site

    Frankfurt, 60596

  • Study site

    Hanover, 30449

  • Study site

    Heidelberg, 69120

  • Study site

    Jena, 07743

  • Study site

    Kiel, 24105

  • Study site

    Leipzig, 04103

  • Study site

    Mainz, 55131

  • Study site

    Minden, 32429

  • Study site

    München, 81377

  • Study site

    Regensburg, 93053

  • Study site

    Tübingen, 72076

  • Study site

    Würzburg, 80337

Other trials in Germany

United Kingdom15 sites

  • Study site

    Cambridge, CB2 2QH

  • Study site

    Edinburgh, EH4 2XU

  • Study site

    Glasgow, G12 0YN

  • Study site

    London, E1 1BB

  • Study site

    London, NW3 2QG

  • Study site

    London, SE1 9RT

  • Study site

    London, SW3 3JJ

  • Study site

    Manchester, M20 4BX

  • Study site

    Newcastle upon Tyne, NE7 7DN

  • Study site

    Northwood, HA6 2RN

  • Study site

    Nottingham, NG5 1PB

  • Study site

    Oxford, OX3 7LJ

  • Study site

    Southampton, SO16 6YD

  • Study site

    Sutton, SM2 5PT

  • Study site

    Swansea, SA2 8QA

Other trials in United Kingdom

Australia11 sites

  • Study site

    Brisbane, 4006

  • Study site

    Frankston, 3199

  • Study site

    Malvern, 3144

  • Study site

    Melbourne, 3002

  • Study site

    Melbourne, 3128

  • Study site

    Nedlands, 6009

  • Study site

    Newcastle, 2310

  • Study site

    St Leonards, 2065

  • Study site

    Sydney, 2060

  • Study site

    Westmead, 2145

  • Study site

    Woolloongabba, 4102

Other trials in Australia

France10 sites

  • Study site

    Bordeaux, 33075

  • Study site

    Lille, 59037

  • Study site

    Marseille, 13005

  • Study site

    Montpellier, 34298

  • Study site

    Nantes, 44093

  • Study site

    Nice, 06202

  • Study site

    Paris, 75010

  • Study site

    Pierre-Bénite, 69495

  • Study site

    Rouen, 76031

  • Study site

    Villejuif, 94805

Other trials in France

Canada8 sites

  • Study site

    Edmonton, Alberta, T5J 3N4

  • Study site

    Hamilton, Ontario, L8V 5C2

  • Study site

    Montreal, Quebec, H3A 1A1

  • Study site

    Montreal, Quebec, H3T 1E2

  • Study site

    Québec, Quebec, G1R 2J6

  • Study site

    Toronto, Ontario, M4N 3M5

  • Study site

    Toronto, Ontario, M5G 2M9

  • Study site

    Winnipeg, Manitoba, R2H 2A6

Other trials in Canada

Italy8 sites

  • Study site

    Bari, 70124

  • Study site

    Genova, 16132

  • Study site

    Milan, 20133

  • Study site

    Milan, 20141

  • Study site

    Milan, 20162

  • Study site

    Naples, 80131

  • Study site

    Roma, 00158

  • Study site

    Siena, 53100

Other trials in Italy

New Zealand5 sites

  • Study site

    Auckland

  • Study site

    Dunedin, 9001

  • Study site

    Hamilton, 2001

  • Study site

    Palmerston North

  • Study site

    Wellington, 6021

Other trials in New Zealand

Sweden5 sites

  • Study site

    Linköping, 58185

  • Study site

    Lund, 22185

  • Study site

    Stockholm, 17176

  • Study site

    Umeå

  • Study site

    Uppsala, 75185

Other trials in Sweden

Israel3 sites

  • Study site

    Jerusalem, 91200

  • Study site

    Ramat Gan, 52621

  • Study site

    Tel Aviv, 64239

Other trials in Israel

Netherlands3 sites

  • Study site

    Amsterdam, 1066 CX

  • Study site

    Amsterdam, 1081 HV

  • Study site

    Groningen, 9713 GZ

Other trials in Netherlands

Switzerland2 sites

  • Study site

    Lausanne, 1011

  • Study site

    Zurich, 8091

Other trials in Switzerland

About this study

Official title: 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

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.

Being tested
Vemurafenib, Dacarbazine
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VemurafenibDrug

    Also called Zelboraf®, RO5185426

    960 mg (as 240 mg tables) orally twice daily

  • DacarbazineDrug

    1000 mg/m2 intravenously every 3 weeks

Study groups in NCT01006980
Study groupRoleWhat they receive
VemurafenibExperimentalNot described
Receives: Drug: Vemurafenib
DacarbazineActive comparatorNot described
Receives: Drug: Dacarbazine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival

    An Overall survival event was defined as death due to any cause. The number of participants with overall survival events is reported.

    Measured: 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).

  2. 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).

    Measured: From randomization (initiated January 2010) to December 30 2010.

Secondary outcomes (6)

  1. 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. Participants who never received study treatment and treated participants 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.

    Measured: From randomization (initiated January 2010) until December 30, 2010

  2. 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 participants who had a best overall response of Complete Response or Partial Response and was estimated using the Kaplan-Meier method.

    Measured: From randomization (initiated in January 2010) until December 30, 2010.

  3. Time to Confirmed Response

    Time to response was defined as the time from randomization to confirmed response (complete response or partial response).

    Measured: From randomization (initiated January 2010) until December 30, 2010.

  4. 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.

    Measured: approximately 3 years

  5. 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.

    Measured: From randomization (initiated January 2010) until December 30, 2010.

  6. 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.

    Measured: 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).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Nov 2009 (estimated)
  2. Study startJan 2010
  3. Primary completionDec 2010
  4. Study completionJul 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
675 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01006980
Sponsor's protocol ID
NO25026
Other IDs
2009-012293-12, 2009
Status last verified
Dec 2015
First submitted
30 Oct 2009
Last updated
28 Sep 2016

Publications

  • 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.

    PubMed 32746839

  • 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.

    PubMed 28961848

  • 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.

    PubMed 25884515

  • 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.

    PubMed 24983357

  • 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.

    PubMed 24508103

  • 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.

    PubMed 23457002

  • 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.

    PubMed 22256804

  • 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.

    PubMed 21639808

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Vemurafenib and Dacarbazine in people with Malignant Melanoma, run by Hoffmann-La Roche at 111 sites in 12 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 111 sites in United States, Germany, United Kingdom, Australia, France and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Nov 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (time frame: 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).). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01006980, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2016.

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