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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01006980




Registration number
NCT01006980
Ethics application status
Date submitted
30/10/2009
Date registered
3/11/2009
Date last updated
28/09/2016

Titles & IDs
Public title
A Study of Vemurafenib (RO5185426) in Comparison With Dacarbazine in Previously Untreated Patients With Metastatic Melanoma (BRIM 3)
Scientific 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
Secondary ID [1] 0 0
2009-012293-12
Secondary ID [2] 0 0
NO25026
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malignant Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Vemurafenib
Treatment: Drugs - Dacarbazine

Experimental: Vemurafenib -

Active comparator: Dacarbazine -


Treatment: Drugs: Vemurafenib
960 mg (as 240 mg tables) orally twice daily

Treatment: Drugs: Dacarbazine
1000 mg/m2 intravenously every 3 weeks
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival
Timepoint [1] 0 0
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).
Primary outcome [2] 0 0
Progression-free Survival
Timepoint [2] 0 0
From randomization (initiated January 2010) to December 30 2010.
Secondary outcome [1] 0 0
Participants With a Best Overall Response (BOR) of Complete Response or Partial Response
Timepoint [1] 0 0
From randomization (initiated January 2010) until December 30, 2010
Secondary outcome [2] 0 0
Duration of Response
Timepoint [2] 0 0
From randomization (initiated in January 2010) until December 30, 2010.
Secondary outcome [3] 0 0
Time to Confirmed Response
Timepoint [3] 0 0
From randomization (initiated January 2010) until December 30, 2010.
Secondary outcome [4] 0 0
Time to Treatment Failure
Timepoint [4] 0 0
approximately 3 years
Secondary outcome [5] 0 0
Number of Participants With Adverse Events (AEs)
Timepoint [5] 0 0
From randomization (initiated January 2010) until December 30, 2010.
Secondary outcome [6] 0 0
Pre and Post-dose Plasma Vemurafenib Concentration by Study Day
Timepoint [6] 0 0
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).

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/01/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/07/2015
Sample size
Target
Accrual to date
Final
675
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Brisbane
Recruitment hospital [2] 0 0
- Frankston
Recruitment hospital [3] 0 0
- Malvern
Recruitment hospital [4] 0 0
- Melbourne
Recruitment hospital [5] 0 0
- Nedlands
Recruitment hospital [6] 0 0
- Newcastle
Recruitment hospital [7] 0 0
- St Leonards
Recruitment hospital [8] 0 0
- Sydney
Recruitment hospital [9] 0 0
- Westmead
Recruitment hospital [10] 0 0
- Woolloongabba
Recruitment postcode(s) [1] 0 0
4006 - Brisbane
Recruitment postcode(s) [2] 0 0
3199 - Frankston
Recruitment postcode(s) [3] 0 0
3144 - Malvern
Recruitment postcode(s) [4] 0 0
3002 - Melbourne
Recruitment postcode(s) [5] 0 0
3128 - Melbourne
Recruitment postcode(s) [6] 0 0
6009 - Nedlands
Recruitment postcode(s) [7] 0 0
2310 - Newcastle
Recruitment postcode(s) [8] 0 0
2065 - St Leonards
Recruitment postcode(s) [9] 0 0
2060 - Sydney
Recruitment postcode(s) [10] 0 0
2145 - Westmead
Recruitment postcode(s) [11] 0 0
4102 - Woolloongabba
Recruitment outside Australia
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Alabama
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Michigan
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Tennessee
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Texas
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Washington
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Alberta
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Ontario
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France
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Nantes
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Paris
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France
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Pierre Benite
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France
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Rouen
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France
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Villejuif
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Germany
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Buxtehude
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Dresden
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Erfurt
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Germany
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Essen
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Frankfurt
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Hannover
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Heidelberg
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Jena
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Koeln
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Leipzig
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Mainz
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Minden
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Muenchen
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Regensburg
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Israel
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Israel
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Ramat Gan
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Israel
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Roma
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Amsterdam
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Groningen
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New Zealand
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Auckland
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Dunedin
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Hamilton
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Palmerston North
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Wellington
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Sweden
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Linkoeping
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Lund
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Stockholm
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Umeå
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Uppsala
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Lausanne
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Zürich
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Cambridge
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Edinburgh
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Manchester
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Newcastle Upon Tyne
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Northwood
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Nottingham
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Oxford
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Southampton
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Sutton
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Swansea

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/study/NCT01006980
Trial related presentations / 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.
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.
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.
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.
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01006980