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NCT01006980 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
COMPLETED
Registry last update
2016-09-28

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Overall Survival

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outcome · POSTED

Progression-free Survival

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outcome · POSTED

Participants With a Best Overall Response (BOR) of Complete Response or Partial Response

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outcome · POSTED

Duration of Response

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outcome · POSTED

Time to Confirmed Response

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outcome · POSTED

Time to Treatment Failure

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outcome · POSTED

Number of Participants With Adverse Events (AEs)

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outcome · POSTED

Pre and Post-dose Plasma Vemurafenib Concentration by Study Day

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
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
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. intervention Names
    1. Drug: Vemurafenib
    label
    Vemurafenib
    type
    EXPERIMENTAL
  2. intervention Names
    1. Drug: Dacarbazine
    label
    Dacarbazine
    type
    ACTIVE_COMPARATOR
interventions
  1. arm Group Labels
    1. Vemurafenib
    description
    960 mg (as 240 mg tables) orally twice daily
    name
    Vemurafenib
    other Names
    1. Zelboraf®
    2. RO5185426
    type
    DRUG
  2. arm Group Labels
    1. Dacarbazine
    description
    1000 mg/m2 intravenously every 3 weeks
    name
    Dacarbazine
    type
    DRUG
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
675
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    An Overall survival event was defined as death due to any cause. The number of participants with overall survival events is reported.
    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).
  2. description
    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).
    measure
    Progression-free Survival
    time Frame
    From randomization (initiated January 2010) to December 30 2010.
secondary Outcomes
  1. description
    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.
    measure
    Participants With a Best Overall Response (BOR) of Complete Response or Partial Response
    time Frame
    From randomization (initiated January 2010) until December 30, 2010
  2. description
    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.
    measure
    Duration of Response
    time Frame
    From randomization (initiated in January 2010) until December 30, 2010.
  3. description
    Time to response was defined as the time from randomization to confirmed response (complete response or partial response).
    measure
    Time to Confirmed Response
    time Frame
    From randomization (initiated January 2010) until December 30, 2010.
  4. description
    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.
    measure
    Time to Treatment Failure
    time Frame
    approximately 3 years
  5. description
    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.
    measure
    Number of Participants With Adverse Events (AEs)
    time Frame
    From randomization (initiated January 2010) until December 30, 2010.
  6. description
    The pharmacokinetics of vemurafenib were assessed at the beginning of each 21-day cycle using pre-dose and 2-4 hours post-dose sampling.
    measure
    Pre and Post-dose Plasma Vemurafenib Concentration by Study Day
    time Frame
    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).
Full study description
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.
Source references
references
  1. citation
    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
    32746839
    type
    DERIVED
  2. citation
    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.
    pmid
    28961848
    type
    DERIVED
  3. citation
    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.
    pmid
    25884515
    type
    DERIVED
  4. citation
    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.
    pmid
    24983357
    type
    DERIVED
  5. citation
    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.
    pmid
    24508103
    type
    DERIVED
  6. citation
    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.
    pmid
    23457002
    type
    DERIVED
  7. citation
    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.
    pmid
    22256804
    type
    DERIVED
  8. citation
    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.
    pmid
    21639808
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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        "><li><strong>Previously untreated patients. </strong>The approval of vemurafenib was supported by an international multicenter trial (<a href="/clinicaltrials/NCT01006980">BRIM-3</a> [NCT01006980]) that screened 2,107 patients with previously untreated stage IIIC or IV melanoma for <em class="gene-name">BRAF</em> V600 pathogeni
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        untreated patients. </strong>The approval of vemurafenib was supported by an international multicenter trial (<a href="/clinicaltrials/NCT01006980">BRIM-3</a> [NCT01006980]) that screened 2,107 patients with previously untreated stage IIIC or IV melanoma for <em class="gene-name">BRAF</em> V600 pathogenic variants and identified
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      source title
      Melanoma Treatment (PDQ®)–Health Professional Version
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      1. context
        Updated: May 2, 2025
        datetime
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    Preserved source evidence · Not medical advice