Trial record 1 of 1 for:    NCT01689519
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A Phase III Study Comparing Vemurafenib vs Vemurafenib Plus Cobimetinib (GDC-0973) in Patients With Metastatic Melanoma (coBRIM)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01689519
First received: September 18, 2012
Last updated: October 1, 2015
Last verified: October 2015
  Purpose
This multicenter, randomized, double-blind, placebo-controlled phase III study will evaluate the safety and efficacy of vemurafenib alone and vemurafenib in combination with cobimetinib (GDC-0973), a mitogen-activated protein kinase (MEK) inhibitor, in previously untreated BRAF V600 mutation-positive patients with unresectable locally advanced or metastatic melanoma. Patients will be randomized to one of two treatment arms, Arm A: vemurafenib 960 mg twice a day (days 1-28 of each cycle) and placebo (days 1-21 of each cycle); Arm B: vemurafenib 960 mg twice a day (days 1-28 of each cycle) and cobimetinib (GDC-0973) 60 mg once daily (days 1-21 of each cycle). Patients will receive treatment until disease progression, unacceptable toxicity, or withdrawal of consent.

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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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.


Enrollment: 495
Study Start Date: January 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Placebo + vemurafenib
Participants received placebo 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: Placebo
Placebo was supplied as tablets.
Drug: Vemurafenib
Vemurafenib was supplied as tablets.
Experimental: Cobimetinib + vemurafenib
Participants received 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 was supplied as tablets.
Drug: Cobimetinib
Cobimetinib was supplied as tablets.
Other Name: GDC-0973

  Eligibility

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

Inclusion Criteria:

  • Patients 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.
  • Patients 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 Response Evaluation Criteria in Solid Tumors (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 ≥ 12 weeks.
  • Adequate hematologic and end organ function.

Exclusion Criteria:

  • History of prior rapidly accelerated fibrosarcoma (RAF) or mitogen-activated protein kinase (MEK) 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. Patients with a previous malignancy within the past 3 years are excluded except for patients with resected basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) 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 (RVO), 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.
  • Patients with active central nervous system (CNS) lesions (including carcinomatous meningitis) are excluded. However, patients 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
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: NCT01689519

  Show 193 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 
Study First Received: September 18, 2012
Results First Received: July 1, 2015
Last Updated: October 1, 2015
Health Authority: United States: Food and Drug Administration

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
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas

ClinicalTrials.gov processed this record on May 26, 2016