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
  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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01006980

  Show 111 Study Locations
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

ClinicalTrials.gov processed this record on October 19, 2014