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

August 19, 2016 updated by: Hoffmann-La Roche

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
675

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Brisbane, Australia, 4006
      • Frankston, Australia, 3199
      • Malvern, Australia, 3144
      • Melbourne, Australia, 3002
      • Melbourne, Australia, 3128
      • Nedlands, Australia, 6009
      • Newcastle, Australia, 2310
      • St Leonards, Australia, 2065
      • Sydney, Australia, 2060
      • Westmead, Australia, 2145
      • Woolloongabba, Australia, 4102
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T5J 3N4
    • Manitoba
      • Winnipeg, Manitoba, Canada, R2H 2A6
    • Ontario
      • Hamilton, Ontario, Canada, L8V 5C2
      • Toronto, Ontario, Canada, M5G 2M9
      • Toronto, Ontario, Canada, M4N 3M5
    • Quebec
      • Montreal, Quebec, Canada, H3A 1A1
      • Montreal, Quebec, Canada, H3T 1E2
      • Quebec City, Quebec, Canada, G1R 2J6
  • France
      • Bordeaux, France, 33075
      • Lille, France, 59037
      • Marseille, France, 13005
      • Montpellier, France, 34298
      • Nantes, France, 44093
      • Nice, France, 06202
      • Paris, France, 75010
      • Pierre Benite, France, 69495
      • Rouen, France, 76031
      • Villejuif, France, 94805
  • Germany
      • Buxtehude, Germany, 21614
      • Dresden, Germany, 01307
      • Erfurt, Germany, 99089
      • Essen, Germany, 45122
      • Frankfurt, Germany, 60596
      • Hannover, Germany, 30449
      • Heidelberg, Germany, 69120
      • Jena, Germany, 07743
      • Kiel, Germany, 24105
      • Koeln, Germany, 50924
      • Leipzig, Germany, 04103
      • Mainz, Germany, 55131
      • Minden, Germany, 32429
      • Muenchen, Germany, 81377
      • Regensburg, Germany, 93053
      • Tuebingen, Germany, 72076
      • Wuerzburg, Germany, 80337
  • Israel
      • Jerusalem, Israel, 91200
      • Ramat Gan, Israel, 52621
      • Tel Aviv, Israel, 64239
  • Italy
      • Bari, Italy, 70124
      • Genova, Italy, 16132
      • Milano, Italy, 20162
      • Milano, Italy, 20133
      • Milano, Italy, 20141
      • Napoli, Italy, 80131
      • Roma, Italy, 00158
      • Siena, Italy, 53100
  • Netherlands
      • Amsterdam, Netherlands, 1081 HV
      • Amsterdam, Netherlands, 1066 CX
      • Groningen, Netherlands, 9713 GZ
  • New Zealand
      • Auckland, New Zealand
      • Dunedin, New Zealand, 9001
      • Hamilton, New Zealand, 2001
      • Palmerston North, New Zealand
      • Wellington, New Zealand, 6021
  • Sweden
      • Linkoeping, Sweden, 58185
      • Lund, Sweden, 22185
      • Stockholm, Sweden, 17176
      • Umeå, Sweden
      • Uppsala, Sweden, 75185
  • Switzerland
      • Lausanne, Switzerland, 1011
      • Zürich, Switzerland, 8091
  • United Kingdom
      • Cambridge, United Kingdom, CB2 2QH
      • Edinburgh, United Kingdom, EH4 2XU
      • Glasgow, United Kingdom, G12 0YN
      • London, United Kingdom, SE1 9RT
      • London, United Kingdom, NW3 2QG
      • London, United Kingdom, E1 1BB
      • London, United Kingdom, SW3 3JJ
      • Manchester, United Kingdom, M20 4BX
      • Newcastle Upon Tyne, United Kingdom, NE7 7DN
      • Northwood, United Kingdom, HA6 2RN
      • Nottingham, United Kingdom, NG5 1PB
      • Oxford, United Kingdom, OX3 7LJ
      • Southampton, United Kingdom, SO16 6YD
      • Sutton, United Kingdom, SM2 5PT
      • Swansea, United Kingdom, SA2 8QA
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35243
    • Arizona
      • Tucson, Arizona, United States, 85724
    • California
      • Los Angeles, California, United States, 90095-1752
      • San Francisco, California, United States, 94117
      • Santa Monica, California, United States, 90404
    • Colorado
      • Aurora, Colorado, United States, 80045
    • Georgia
      • Atlanta, Georgia, United States, 30322
    • Indiana
      • Indianapolis, Indiana, United States, 46202
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
      • Boston, Massachusetts, United States, 02114
      • Boston, Massachusetts, United States, 02115
    • Michigan
      • Detroit, Michigan, United States, 48201
    • Missouri
      • St Louis, Missouri, United States, 63110
    • New York
      • New York, New York, United States, 10016
      • New York, New York, United States, 10065
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27514
    • Oregon
      • Portland, Oregon, United States, 97213
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
      • Pittsburgh, Pennsylvania, United States, 15213-2584
    • Tennessee
      • Nashville, Tennessee, United States, 37232
      • Nashville, Tennessee, United States, 37203
    • Texas
      • Dallas, Texas, United States, 75246
    • Utah
      • Salt Lake City, Utah, United States, 84112
    • Washington
      • Seattle, Washington, United States, 98109

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Dacarbazine
Drug: Dacarbazine
1000 mg/m2 intravenously every 3 weeks
Experimental: Vemurafenib
Drug: Vemurafenib
960 mg (as 240 mg tables) orally twice daily
Other Names:
  • RO5185426
  • Zelboraf®

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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).
An Overall survival event was defined as death due to any cause. The number of participants with overall survival events is reported.
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).
Progression-free Survival
Time Frame: From randomization (initiated January 2010) to December 30 2010.
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).
From randomization (initiated January 2010) to December 30 2010.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Participants With a Best Overall Response (BOR) of Complete Response or Partial Response
Time Frame: From randomization (initiated January 2010) until December 30, 2010
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.
From randomization (initiated January 2010) until December 30, 2010
Duration of Response
Time Frame: From randomization (initiated in January 2010) until December 30, 2010.
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.
From randomization (initiated in January 2010) until December 30, 2010.
Time to Confirmed Response
Time Frame: From randomization (initiated January 2010) until December 30, 2010.
Time to response was defined as the time from randomization to confirmed response (complete response or partial response).
From randomization (initiated January 2010) until December 30, 2010.
Time to Treatment Failure
Time Frame: approximately 3 years
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.
approximately 3 years
Number of Participants With Adverse Events (AEs)
Time Frame: From randomization (initiated January 2010) until December 30, 2010.
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.
From randomization (initiated January 2010) until December 30, 2010.
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).
The pharmacokinetics of vemurafenib were assessed at the beginning of each 21-day cycle using pre-dose and 2-4 hours post-dose sampling.
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).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hoffmann-La Roche

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2010

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2010

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 30, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 2, 2009

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 3, 2009

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 28, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 19, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NO25026
  • 2009-012293-12

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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