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

April 1, 2022 updated by: Hoffmann-La Roche

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

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.

Study Overview

Status

Completed

Conditions

Study Type

Interventional

Enrollment (Actual)

495

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • Chris O'Brien Lifehouse
      • Gateshead, New South Wales, Australia, 2290
        • Lake Macquarie Private Hospital
      • Lismore, New South Wales, Australia, 2480
        • Lismore Base Hospital; Cancer Care & Haematology Unit
      • North Sydney, New South Wales, Australia, 2060
        • Melanoma Institute Australia
      • Woolloongabba, New South Wales, Australia, 2050
        • Princess Alexandra Hospital
    • Northern Territory
      • Casuarina, Northern Territory, Australia, 0811
        • Royal Darwin Hospital
    • Queensland
      • Greenslopes, Queensland, Australia, 4120
        • Greenslopes Private Hospital
      • Herston, Queensland, Australia, 4029
        • Royal Brisbane and Women's Hospital
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Royal Adelaide Hospital; Hepatology
      • Ashford SA, South Australia, Australia, 5035
        • Ashford Cancer Centre
    • Tasmania
      • Hobart, Tasmania, Australia, 7000
        • Royal Hobart Hospital
      • Launceston, Tasmania, Australia, 7250
        • Launceston General Hospital; Gastroenterology Research
    • Victoria
      • Frankston, Victoria, Australia, 3199
        • Peninsula and South Eastern Haematology and Oncology Group
      • Heidelberg, Victoria, Australia, 3084
        • Austin Hospital
      • Melbourne, Victoria, Australia, 3000
        • Peter MacCallum Cancer Centre-East Melbourne
      • Prahan, Victoria, Australia, 3181
        • The Alfred Hospital
    • Western Australia
      • Murdoch, Western Australia, Australia, 6150
        • Fiona Stanley Hospital
      • Linz, Austria, 4020
        • Ordensklinikum Linz Elisabethinen
      • St. Pölten, Austria, 3100
        • Landesklinikum St. Pölten
      • Wien, Austria, 1090
        • Medizinische Universitat Wien
      • Bruxelles, Belgium, 1200
        • Cliniques Universitaires St-Luc
      • Bruxelles, Belgium, 1000
        • Institut Jules Bordet; Department of Medical Oncology
      • Edegem, Belgium, 2650
        • UZ Antwerpen
      • Hasselt, Belgium, 3500
        • Jessa Zkh (Campus Virga Jesse)
      • Liège, Belgium, 4000
        • CHU Sart-Tilman
      • Roeselare, Belgium, 8800
        • AZ Delta (Campus Rumbeke)
    • British Columbia
      • Victoria, British Columbia, Canada, V8R 6V5
        • BC Cancer Agency Vancouver Island Cancer Centre
    • Ontario
      • Hamilton, Ontario, Canada, L8V 5C2
        • Juravinski Cancer Clinic; Department of Oncology
      • Ottawa, Ontario, Canada, K1H 1C4
        • The Ottawa Hospital Cancer Center; General Campus
      • Toronto, Ontario, Canada, M4N 3M5
        • Toronto Sunnybrook Hospital
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Hospital; Department of Med Oncology
    • Quebec
      • London, Quebec, Canada, N6A 4G5
        • London Health Sciences Centre · Victoria Hospital;Department of Pediatrics
      • Montréal, Quebec, Canada, H2W 1S6
        • McGill University Health Centre/Glen Site / Royal Victoria Hospital
      • Brno, Czechia, 656 53
        • Masarykuv onkologicky ustav
      • Hradec Kralove, Czechia, 500 05
        • Fakultni nemocnice Hradec Kralove
      • Olomouc, Czechia, 775 20
        • Fakultní nemocnice Olomouc
      • Ostrava - Poruba, Czechia, 708 52
        • Fakultni nemocnice Ostrava
      • Pardubice, Czechia, 532 03
        • Multiscan s.r.o.
      • Prague, Czechia, 180 01
        • Nemocnice Na Bulovce
      • Praha, Czechia, 100 34
        • Fakultni nemocnice Kralovske Vinohrady
      • Praha, Czechia, 150 06
        • Fakultni nemocnice Motol; Neurologicka klinika
      • Praha 2, Czechia, 128 08
        • Vseobecna fakultni nemocnice v Praze
      • Bordeaux, France, 33075
        • Groupe Hospitalier Saint André - Hôpital Saint André
      • Boulogne Billancourt, France, 92104
        • Hôpital Ambroise Paré - Boulogne-Billancourt; Respiratory
      • Clermont Ferrand cedex 1, France, 63003
        • CHU Clermont Ferrand - Hôpital d'Estaing
      • Dijon, France, 21000
        • CHU de Dijon - Hopital le Bocage
      • La Tronche, France, 38700
        • Centre Hospitalier Universitaire de Grenoble - Albert Michallon
      • Lille, France, 59037
        • Hopital Claude Huriez - CHU Lille
      • Marseille, France, 13005
        • Hopital de La Timone
      • Montpellier, France, 34295
        • Hopital Saint Eloi
      • Nantes, France, 44093
        • CHU NANTES - Hôtel Dieu; Pharmacy
      • Nice, France, 06202
        • CHU Nice - Hôpital de l'Archet 2
      • Pierre Benite, France, 69495
        • Centre Hospitalier Lyon Sud
      • Reims, France, 51092
        • Hopital Robert Debre; DERMATOLOGIE
      • Rennes, France, 35042
        • Centre Eugene Marquis; Service d'oncologie
      • Bochum, Germany, 44791
        • St. Josef-Hospital; Studienambulanz
      • Buxtehude, Germany, 21614
        • Elbekliniken Buxtehude GmbH
      • Dresden, Germany, 01307
        • Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden
      • Erfurt, Germany, 99089
        • HELIOS Klinikum Erfurt
      • Essen, Germany, 45147
        • Universitatsklinikum Essen
      • Freiburg, Germany, 79106
        • Universitaetsklinikum Freiburg
      • Gera, Germany, 07548
        • SRH Wald-Klinikum Gera; Klinik für Hautkrankheiten und Allergologie
      • Göttingen, Germany, 37075
        • Universitatsmedizin Gottingen
      • Hamburg, Germany, 20246
        • Universitätsklinikum Hamburg-Eppendorf
      • Hannover, Germany, 30625
        • Medizinische Hochschule Hannover
      • Heidelberg, Germany, 69120
        • Universitätsklinikum Heidelberg
      • Kiel, Germany, 24105
        • Universitaetsklinikum Schleswig-Holstein - Campus Kiel; Klinik fuer Allgemeine Innere Medizin
      • Koeln, Germany, 50937
        • Universitaetsklinikum Koeln; Hematology/Oncology
      • Mainz, Germany, 55101
        • Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
      • Mannheim, Germany, 68167
        • Klinikum Mannheim GmbH Universitätsklinikum
      • Muenster, Germany, 48157
        • Fachklinik Hornheide
      • München, Germany, 80337
        • Klinikum der Ludwigs-Maximilians-Universitaet Muenchen
      • Regensburg, Germany, 93053
        • Universitaetsklinikum Regensburg
      • Tuebingen, Germany, 72076
        • Universitatsklinikum Tubingen
      • Würzburg, Germany, 97080
        • Universitatsklinikum Wurzburg
      • Budapest, Hungary, 1122
        • Orszagos Onkologiai Intezet
      • Gyula, Hungary, 5700
        • Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaza
      • Pecs, Hungary, 7624
        • Somogy Megyei Kaposi Mór Oktató Kórház
      • Szeged, Hungary, 6720
        • Szegedi Tud.Egyetem Szent-Gyorgyi Albert Klin.Kozp.
      • Beer Sheva, Israel, 8410100
        • Soroka Medical Center; Oncology Dept
      • Haifa, Israel, 3109600
        • Rambam Health Care Campus
      • Jerusalem, Israel, 9112000
        • HADASSAH UNIVERSITY HOSPITAL, EIN KAREM; Oncology
      • Petach Tikva, Israel, 4941492
        • Rabin Medical Center-Beilinson Campus;Hematology-Oncology
      • Ramat Gan, Israel, 5265601
        • Chaim Sheba Medical Center
      • Tel Aviv, Israel, 6423906
        • Tel Aviv Sourasky MC, Dana children's hospital;Oncology Division
    • Campania
      • Napoli, Campania, Italy, 80131
        • Istituto Nazionale Tumori Fondazione G. Pascale
    • Emilia-Romagna
      • Meldola, Emilia-Romagna, Italy, 47014
        • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
      • Modena, Emilia-Romagna, Italy, 40124
        • A.O.U. Policlinico di Modena
    • Lazio
      • Roma, Lazio, Italy, 00144
        • Istituto Nazionale Tumori Regina Elena Irccs
    • Liguria
      • Genova, Liguria, Italy, 16132
        • Istituto Nazionale per la Ricerca sul Cancro di Genova
    • Lombardia
      • Bergamo, Lombardia, Italy, 24127
        • Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)
      • Brescia, Lombardia, Italy, 25100
        • Asst Degli Spedali Civili Di Brescia
      • Milano, Lombardia, Italy, 20133
        • Fondazione IRCCS Istituto Nazionale dei Tumori
    • Puglia
      • Bari, Puglia, Italy, 70126
        • Istituto Tumori Giovanni Paolo II IRCSS; Ospedale Oncologico Bari
    • Toscana
      • Siena, Toscana, Italy, 53100
        • A.O.U. Senese Policlinico Santa Maria alle Scotte
    • Veneto
      • Padova, Veneto, Italy, 35128
        • Iov - Istituto Oncologico Veneto Irccs
      • Amsterdam, Netherlands, 1081 HV
        • Amsterdam UMC Location VUMC
      • Leiden, Netherlands, 2333 ZA
        • Leids Universitair Medisch Centrum; Cardiology
      • Maastricht, Netherlands, 6229 HX
        • Maastricht University Medical Center
      • Auckland, New Zealand, 1023
        • Auckland City Hospital
      • Hamilton, New Zealand, 3248
        • Waikato Hospital
      • Oslo, Norway, 0379
        • Radiumhospitalet
      • Barnaul, Russian Federation, 656045
        • TSBHI Altai Territorial oncological dispensary
      • Moscow, Russian Federation, 143423
        • Moscow city oncology hospital #62 of Moscow Healthcare Department
      • Moscow, Russian Federation, 115478
        • FSBSI "N. N. Blokhin Russian Cancer Research Center"
      • Omsk, Russian Federation, 644013
        • BHI of Omsk region Clinical Oncology Dispensary
      • Pyatigorsk, Russian Federation, 357524
        • Pyatigorsky Oncologic Dispensary
      • Barcelona, Spain, 08036
        • Hospital Clinic I Provincial de Barcelona
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain, 28033
        • MD Anderson Cancer Center
      • Valencia, Spain, 46014
        • Hospital General Universitario de Valencia
      • Zaragoza, Spain, 50009
        • Hospital Universitario Miguel Servet
    • LA Coruña
      • Santiago de Compostela, LA Coruña, Spain, 15706
        • Complexo Hospitalario Universitario De Santiago
    • Navarra
      • Pamplona, Navarra, Spain, 31008
        • Clinica Universitaria de Navarra
    • Sevilla
      • Seville, Sevilla, Spain, 41071
        • Hospital Universitario Virgen Macarena
      • Jönköping, Sweden, 551 85
        • Länssjukhuset Ryhov
      • Lund, Sweden, 221 85
        • Skanes universitetssjukhus
      • Mölnlycke, Sweden, 435 33
        • Sahlgrenska Sjukhuset
      • Uppsala, Sweden, 751 85
        • Akademiska Sjukhuset
      • Bern, Switzerland, 3010
        • Inselspital-Universitaetsspital Bern
      • Chur, Switzerland, 7000
        • Kantonsspital Graubuenden
      • Bristol, United Kingdom, BS2 8ED
        • Bristol Haematology and Oncology Centre
      • Cambridge, United Kingdom, CB2 0QQ
        • Addenbrooke's Hospital
      • Cardiff, United Kingdom, CF14 2TL
        • Velindre Cancer Centre
      • Edinburgh, United Kingdom, EH4 2XU
        • Western General Hospital
      • Glasgow, United Kingdom, G12 0YN
        • Beatson West of Scotland Cancer Centre
      • Liverpool, United Kingdom, L7 8YA
        • The Clatterbridge Cancer Centre NHS Foundation Trust
      • London, United Kingdom, EC1A 7BE
        • Barts and the London NHS Trust.
      • London, United Kingdom, SW3 6JJ
        • Royal Marsden Hospital - London
      • London, United Kingdom, SW3 6JJ
        • Royal Marsden Hospital - Fulham
      • London, United Kingdom, SW17 0QT
        • St George's Hospital; Courtyard Clinic
      • Newcastle upon Tyne, United Kingdom, NE7 7DN
        • Freeman Hospital
      • Nottingham, United Kingdom, NG7 2UH
        • Nottingham University Hospitals; QMC Campus
      • Southampton, United Kingdom, SO16 6YD
        • Southampton General Hospital
      • Truro, United Kingdom, TR1 3LQ
        • Royal Cornwall Hospital
      • Wolverhampton, United Kingdom, WV10 0QP
        • New Cross Hospital
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham
    • California
      • Los Angeles, California, United States, 90025
        • The Angeles Clinic and Research Institute - W LA Office
      • Sacramento, California, United States, 95817
        • University of California Davis Health System
      • Santa Rosa, California, United States, 95403
        • Sutter Pacific Medical Foundation
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado
    • Florida
      • Fort Myers, Florida, United States, 33901
        • Florida Cancer Specialists - Broadway
      • Miami Beach, Florida, United States, 33140
        • Mount Sinai Medical Center
      • Orlando, Florida, United States, 32806
        • Orlando Health Inc.
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern Center for Clinical Research
    • Kansas
      • Kansas City, Kansas, United States, 66160-7314
        • Uni of Kansas Medical Center; Dept of Neurology
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • U of L - Physicians Pulmonology; Dept of Neuroradiology and Dept of Diagnostic Radiology
    • Missouri
      • Saint Louis, Missouri, United States, 63108
        • Washington University School of Medicine; Dept of Medicine/Div of Medical Oncology
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth-Hitchcock Medical Center; Department of Medicine
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27103
        • Novant Health Oncology Specialists
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • University Hospitals of Cleveland
    • Pennsylvania
      • Bethlehem, Pennsylvania, United States, 18015
        • St. Luke's University Health network
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University Hospital
      • Pittsburgh, Pennsylvania, United States, 15261
        • University of Pittsburgh
    • Rhode Island
      • Providence, Rhode Island, United States, 2903
        • Rhode Island Hospital; Investigational Services
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Placebo supplied as tablets
Vemurafenib supplied as tablets
Other Names:
  • 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.
Vemurafenib supplied as tablets
Other Names:
  • RO518426
Cobimetinib supplied as tablets
Other Names:
  • RO5514041
  • GDC-0973
  • XL518

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline to the 21 July 2019 data cut-off (up to 7 years, 6 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline to the 21 July 2019 data cut-off (up to 7 years, 6 months)
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.
Baseline to the 21 July 2019 data cut-off (up to 7 years, 6 months)
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.
Baseline to the 21 July 2019 data cut-off (up to 7 years, 6 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 8, 2013

Primary Completion (Actual)

May 9, 2014

Study Completion (Actual)

July 21, 2019

Study Registration Dates

First Submitted

September 18, 2012

First Submitted That Met QC Criteria

September 18, 2012

First Posted (Estimate)

September 21, 2012

Study Record Updates

Last Update Posted (Actual)

May 2, 2022

Last Update Submitted That Met QC Criteria

April 1, 2022

Last Verified

April 1, 2022

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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