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Trial details imported from ClinicalTrials.gov

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




Trial ID
NCT01006980
Ethics application status
Date submitted
30/10/2009
Date registered
2/11/2009
Date last updated
19/08/2016

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 - An Overall survival event was defined as death due to any cause. The number of participants with overall survival events is reported.
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 - 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).
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 - 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.
Timepoint [1] 0 0
From randomization (initiated January 2010) until December 30, 2010
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
From randomization (initiated in January 2010) until December 30, 2010.
Secondary outcome [3] 0 0
Time to Confirmed Response - Time to response was defined as the time from randomization to confirmed response (complete response or partial response).
Timepoint [3] 0 0
From randomization (initiated January 2010) until December 30, 2010.
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
approximately 3 years
Secondary outcome [5] 0 0
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.
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 - The pharmacokinetics of vemurafenib were assessed at the beginning of each 21-day cycle using pre-dose and 2-4 hours post-dose sampling.
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
Gender
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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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United States of America
State/province [1] 0 0
Alabama
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Arizona
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Colorado
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Indiana
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Massachusetts
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Michigan
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Missouri
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New York
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North Carolina
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Oregon
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Pennsylvania
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Tennessee
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Texas
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Utah
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Washington
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Canada
State/province [18] 0 0
Alberta
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Canada
State/province [19] 0 0
Manitoba
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Canada
State/province [20] 0 0
Ontario
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Canada
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Quebec
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France
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Bordeaux
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France
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Lille
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France
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Marseille
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France
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Montpellier
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France
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Nantes
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France
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Nice
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France
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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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Essen
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Heidelberg
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Jena
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Kiel
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Koeln
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Leipzig
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Mainz
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Germany
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Minden
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Muenchen
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Germany
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Regensburg
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Germany
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Tuebingen
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Germany
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Wuerzburg
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Israel
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Jerusalem
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Israel
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Ramat Gan
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Israel
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Tel Aviv
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Bari
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Napoli
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Roma
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Siena
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Amsterdam
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Groningen
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Auckland
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Dunedin
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Hamilton
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Wellington
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Linkoeping
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Lund
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Stockholm
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Lausanne
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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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United Kingdom
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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/show/NCT01006980
Trial related presentations / publications
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