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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01006980
First received: October 30, 2009
Last updated: December 18, 2012
Last verified: December 2012
History of Changes
  Purpose

This randomized, open-label study will evaluate the efficacy, safety and tolerability of RO5185426 as compared to dacarbazine in previously untreated patients with metastatic melanoma. Patients will be randomized to receive either RO5185426 [RG7204; PLEXXIKON: PLX4032] 960 mg orally twice daily or dacarbazine 1000 mg/m2 intravenously every 3 weeks. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs. Patients in the dacarbazine arm may cross over to RO5185426 treatment.


Condition Intervention Phase
Malignant Melanoma
 Drug: RO5185426
Drug: dacarbazine
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: BRIM 3: A Randomized, Open-label, Controlled, Multicenter, Global Study on Progression-free and Overall Survival in Previously Untreated Patients With Unresectable Stage IIIC or Stage IV Melanoma With V600E BRAF Mutation Receiving RO5185426 or Dacarbazine

Resource links provided by NLM:

MedlinePlus related topics: Melanoma
Drug Information available for: Dacarbazine
U.S. FDA Resources

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • 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). ] [ Designated as safety issue: No ]
    An Overall survival event was defined as death due to any cause. The number of participants with overall survival events is reported.

  • Progression-free Survival [ Time Frame: From randomization (initiated January 2010) to December 30 2010. ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Participants With a Best Overall Response (BOR) of Complete Response or Partial Response [ Time Frame: From randomization (initiated January 2010) until December 30, 2010 ] [ Designated as safety issue: No ]
    BOR was defined as a complete response (CR) or partial response (PR) confirmed per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Patients who never received study treatment and treated patients 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.

  • Duration of Response [ Time Frame: From randomization (initiated in January 2010) until December 30, 2010. ] [ Designated as safety issue: No ]
    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 patients who had a best overall response of Complete Response or Partial Response and was estimated using the Kaplan-Meier method.

  • Time to Confirmed Response [ Time Frame: From randomization (initiated January 2010) until December 30, 2010. ] [ Designated as safety issue: No ]
    Time to response was defined as the time from randomization to confirmed response (complete response or partial response).

  • Time to Treatment Failure [ Time Frame: approximately 3 years ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Adverse Events (AEs) [ Time Frame: From randomization (initiated January 2010) until December 30, 2010. ] [ Designated as safety issue: No ]
    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.

  • 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). ] [ Designated as safety issue: No ]
    The pharmacokinetics of vemurafenib were assessed at the beginning of each 21-day cycle using pre-dose and 2-4 hours post-dose sampling.


Enrollment: 677
Study Start Date: January 2010
Estimated Study Completion Date: June 2014
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: RO5185426
960 mg orally twice daily
Active Comparator: B Drug: dacarbazine
1000 mg/m2 iv every 3 weeks

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • adult patients, >/=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 CNS 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01006980

  Hide Study Locations
Locations
United States, Alabama
Birmingham, Alabama, United States, 35243
United States, Arizona
Tucson, Arizona, United States, 85724
United States, California
Los Angeles, California, United States, 90095-1752
San Francisco, California, United States, 94117
Santa Monica, California, United States, 90404
United States, Colorado
Aurora, Colorado, United States, 80045
United States, Georgia
Atlanta, Georgia, United States, 30322
United States, Indiana
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
Boston, Massachusetts, United States, 02114
Boston, Massachusetts, United States, 02215
Boston, Massachusetts, United States, 02115
United States, Michigan
Detroit, Michigan, United States, 48201
United States, Missouri
St Louis, Missouri, United States, 63110
United States, New York
New York, New York, United States, 10016
New York, New York, United States, 10065
United States, North Carolina
Chapel Hill, North Carolina, United States, 27514
United States, Oregon
Portland, Oregon, United States, 97213
United States, Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Pittsburgh, Pennsylvania, United States, 15213-2584
United States, Tennessee
Nashville, Tennessee, United States, 37232
Nashville, Tennessee, United States, 37203
United States, Texas
Dallas, Texas, United States, 75246
United States, Utah
Salt Lake City, Utah, United States, 84112
United States, Washington
Seattle, Washington, United States, 98109
Australia
Brisbane, Australia, 4006
Frankston, Australia, 3199
Malvern, Australia, 3144
Melbourne, Australia, 3128
Melbourne, Australia, 3002
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
Canada, Manitoba
Winnipeg, Manitoba, Canada, R2H 2A6
Canada, Ontario
Hamilton, Ontario, Canada, L8V 5C2
Toronto, Ontario, Canada, M4N 3M5
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Montreal, Quebec, Canada, H3T 1E2
Montreal, Quebec, Canada, H3A 1A1
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, 20141
Milano, Italy, 20162
Milano, Italy, 20133
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, SW3 3JJ
London, United Kingdom, E1 1BB
London, United Kingdom, SE1 9RT
London, United Kingdom, NW3 2QG
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
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided by Hoffmann-La Roche

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01006980     History of Changes
Other Study ID Numbers: NO25026, 2009-012293-12
Study First Received: October 30, 2009
Results First Received: July 29, 2011
Last Updated: December 18, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
 Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 21, 2013