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A Study Comparing Vemurafenib Versus Vemurafenib Plus Cobimetinib in Participants With Metastatic Melanoma (coBRIM)

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ClinicalTrials.gov Identifier: NCT01689519
Recruitment Status : Completed
First Posted : September 21, 2012
Results First Posted : October 30, 2015
Last Update Posted : September 16, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE September 18, 2012
First Posted Date  ICMJE September 21, 2012
Results First Submitted Date  ICMJE July 1, 2015
Results First Posted Date  ICMJE October 30, 2015
Last Update Posted Date September 16, 2020
Actual Study Start Date  ICMJE January 8, 2013
Actual Primary Completion Date May 9, 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 14, 2020)
Progression-free Survival [ Time Frame: Baseline to the 21 July 2019 data cut-off (up to 7 years, 6 months) ]
Progression-free survival was defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator using Response Evaluation Criteria in Solid Tumors v1.1, or death from any cause, whichever came first. Disease progression was defined as: (1) at least a 20% increase in the sum (the increase in the sum must be at least 5 mm) of diameters of target lesions, taking as reference the smallest sum during the study; (2) unequivocal progression of existing non-target lesions; or (3) the appearance of 1 or more new lesions.
Original Primary Outcome Measures  ICMJE
 (submitted: September 18, 2012)
Progression-free survival according to Response Evaluation Criteria in Solid Tumors v1.1 [ Time Frame: Approximately 5 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 14, 2020)
  • Overall Survival [ Time Frame: Baseline to the 21 July 2019 data cut-off (up to 7 years, 6 months) ]
    Overall survival was defined as the time from randomization until the date of death from any cause.
  • Percentage of Participants With an Objective Response [ Time Frame: Baseline to the 21 July 2019 data cut-off (up to 7 years, 6 months) ]
    An objective response was defined as a complete response or a partial response determined on two consecutive occasions ≥ 4 weeks apart. Responses were determined by Response Evaluation Criteria in Solid Tumors v1.1. A complete response was defined as the disappearance of all target lesions or the disappearance of all non-target lesions and normalization of tumor marker level. A partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter of target lesions.
  • Duration of Response [ Time Frame: Baseline to the 21 July 2019 data cut-off (up to 7 years, 6 months) ]
    Duration of response was defined as the time from first occurrence of a documented confirmed objective response until the time of disease progression, as determined by investigator review of tumor assessments using Response Evaluation Criteria in Solid Tumors v1.1 or death from any cause during the study. Disease progression was defined as: (1) at least a 20% increase in the sum (the increase in the sum must be at least 5 mm) of diameters of target lesions, taking as reference the smallest sum during the study; (2) unequivocal progression of existing non-target lesions; or (3) the appearance of 1 or more new lesions.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 18, 2012)
  • Overall survival [ Time Frame: Approximately 5 years ]
  • Objective response rate according to Response Evaluation Criteria in Solid Tumors v1.1 [ Time Frame: Approximately 5 years ]
  • Duration of response according to Response Evaluation Criteria in Solid Tumors v1.1 [ Time Frame: Approximately 5 years ]
  • Safety: incidence of adverse events [ Time Frame: Approximately 5 years ]
  • Pharmacokinetics: Area under the plasma concentration time curve trough 24 hours [ Time Frame: Cycle 1, days 1 and 15; cycle 2, day 15 ]
  • Pharmacokinetics: Minimum observed plasma concentration [ Time Frame: Cycle 1, days 1 and 15; cycle 2, day 15 ]
  • Pharmacokinetics: Apparent clearance following oral dosing [ Time Frame: Cycle 1, days 1 and 15; cycle 2, day 15 ]
  • Quality of life as measured by the European Organization for Research and Cancer Quality of Life Questionnaire (QLQ-30) [ Time Frame: Approximately 5 years ]
  • Quality of life as measured by the EuroQol 5 dimension (EQ-5D) [ Time Frame: Approximately 5 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Comparing Vemurafenib Versus Vemurafenib Plus Cobimetinib in Participants With Metastatic Melanoma
Official Title  ICMJE A Phase III, Double-Blind, Placebo-Controlled Study of Vemurafenib Versus Vemurafenib Plus GDC-0973 in Previously Untreated BRAF^600-Mutation Positive Patients With Unresectable Locally Advanced or Metastatic Melanoma
Brief Summary To evaluate the efficacy of vemurafenib in combination with cobimetinib (GDC-0973), compared with vemurafenib and placebo, in previously untreated BRAF V600 mutation-positive patients with unresectable locally advanced or metastatic melanoma, as measured by progression-free survival (PFS), assessed by the study site investigator.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Malignant Melanoma
Intervention  ICMJE
  • Drug: Placebo
    Placebo supplied as tablets
  • Drug: Vemurafenib
    Vemurafenib supplied as tablets
    Other Name: RO518426
  • Drug: Cobimetinib
    Cobimetinib supplied as tablets
    Other Names:
    • GDC-0973
    • RO5514041
    • XL518
Study Arms  ICMJE
  • Active Comparator: Placebo + Vemurafenib
    Participants will receive placebo orally once daily on Days 1-21 of each 28-day cycle plus vemurafenib 960 milligrams (mg) orally twice a day on Days 1-28 of each 28-day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.
    Interventions:
    • Drug: Placebo
    • Drug: Vemurafenib
  • Experimental: Cobimetinib + Vemurafenib
    Participants will receive cobimetinib 60 mg orally once daily on Days 1-21 of each 28-day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28-day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.
    Interventions:
    • Drug: Vemurafenib
    • Drug: Cobimetinib
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 1, 2015)
495
Original Estimated Enrollment  ICMJE
 (submitted: September 18, 2012)
500
Actual Study Completion Date  ICMJE July 21, 2019
Actual Primary Completion Date May 9, 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Participants with histologically confirmed melanoma, either unresectable stage IIIc or stage IV metastatic melanoma, as defined by the American Joint Committee on Cancer 7th edition. Unresectability of stage IIIc disease must have confirmation from a surgical oncologist
  • Participants must be naïve to treatment for locally advanced unresectable or metastatic disease (ie, no prior systemic anti-cancer therapy for advanced disease; stage IIIc and IV). Prior adjuvant immunotherapy (including ipilimumab) is allowed
  • Documentation of BRAF V600 mutation-positive status in melanoma tumor tissue (archival or newly obtained tumor samples) using the cobas 4800 BRAF V600 mutation test
  • Measurable disease per RECIST v1.1
  • Eastern Clinical Oncology Group performance status of 0 or 1
  • Consent to provide archival for biomarker analyses
  • Consent to undergo tumor biopsies for biomarker analyses
  • Life expectancy greater than or equal to (≥) 12 weeks
  • Adequate hematologic and end organ function

Exclusion Criteria:

  • History of prior rapidly accelerated fibrosarcoma or mitogen-activated protein kinase pathway inhibitor treatment
  • Palliative radiotherapy within 14 days prior to the first dose of study treatment
  • Major surgery or traumatic injury within 14 days prior to first dose of study treatment
  • Active malignancy other than melanoma that could potentially interfere with the interpretation of efficacy measures. Participants with a previous malignancy within the past 3 years are excluded except for participants with resected basal cell carcinoma or squamous cell carcinoma of the skin, melanoma in-situ, carcinoma in-situ of the cervix, and carcinoma in-situ of the breast
  • History of or evidence of retinal pathology on ophthalmological examination that is considered a risk factor for neurosensory retinal detachment, retinal vein occlusion, or neovascular macular degeneration
  • Uncontrolled glaucoma with intraocular pressure
  • Serum cholesterol ≥ Grade 2
  • Hypertriglyceridemia ≥ Grade 2
  • Hyperglycemia (fasting) ≥ Grade 2
  • History of clinically significant cardiac dysfunction
  • Participants with active central nervous system (CNS) lesions (including carcinomatous meningitis) are excluded. However, participants are eligible if:

    1. All known CNS lesions have been treated with stereotactic therapy or surgery, AND
    2. There has been no evidence of clinical and radiographic disease progression in the CNS for ≥ 3 weeks after radiotherapy or surgery
  • Current severe, uncontrolled systemic disease
  • History of malabsorption or other condition that would interfere with absorption of study drugs
  • Pregnant, lactating, or breast feeding women
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Canada,   Czechia,   France,   Germany,   Hungary,   Israel,   Italy,   Netherlands,   New Zealand,   Norway,   Russian Federation,   Spain,   Sweden,   Switzerland,   United Kingdom,   United States
Removed Location Countries Czech Republic,   Turkey
 
Administrative Information
NCT Number  ICMJE NCT01689519
Other Study ID Numbers  ICMJE GO28141
2012-003008-11 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP