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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01689519
First Posted: September 21, 2012
Last Update Posted: September 28, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Hoffmann-La Roche
  Purpose
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.

Condition Intervention Phase
Malignant Melanoma Drug: Placebo Drug: Vemurafenib Drug: Cobimetinib Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Progression-free Survival [ Time Frame: Baseline to the 09 May 2014 data cut-off (up to 1 year, 4 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.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: Baseline to the 09 May 2014 data cut-off (up to 1 year, 4 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 09 May 2014 data cut-off (up to 1 year, 4 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 09 May 2014 data cut-off (up to 1 year, 4 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.

  • Overall Survival (Final Analysis) [ Time Frame: Baseline to the 28 August 2015 Overall Survival data cut-off (up to 2 years, 8 months) ]
    Overall survival was defined as the time from randomization until the date of death from any cause.


Enrollment: 495
Actual Study Start Date: January 9, 2013
Estimated Study Completion Date: December 31, 2019
Primary Completion Date: May 9, 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Placebo
Placebo supplied as tablets
Drug: Vemurafenib
Vemurafenib supplied as tablets
Other Name: RO518426
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.
Drug: Vemurafenib
Vemurafenib supplied as tablets
Other Name: RO518426
Drug: Cobimetinib
Cobimetinib supplied as tablets
Other Names:
  • GDC-0973
  • RO5514041
  • XL518

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01689519


  Show 194 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01689519     History of Changes
Other Study ID Numbers: GO28141
2012-003008-11 ( EudraCT Number )
First Submitted: September 18, 2012
First Posted: September 21, 2012
Results First Submitted: July 1, 2015
Results First Posted: October 30, 2015
Last Update Posted: September 28, 2017
Last Verified: September 2017

Keywords provided by Hoffmann-La Roche:
Zelboraf
vemurafenib
RG7204
PLX4032
Genentech MEK inhibitor
Genentech BRAF inhibitor
Roche MEK inhibitor
Roche BRAF inhibitor
RO5185426
metastatic melanoma
BRAF positive melanoma
BRAF mutant melanoma
advanced melanoma
Genentech RAF inhibitor
Roche RAF inhibitor
BRAF V600E kinase inhibitor
Oncogenic BRAF inhibitor
BRAF kinase inhibitor
GDC-0973
XL518
melanoma

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
Vemurafenib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action