A Study Comparing Vemurafenib Versus Vemurafenib Plus Cobimetinib in Participants With Metastatic Melanoma
NCT ID: NCT01689519
Last Updated: 2022-05-02
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
495 participants
INTERVENTIONAL
2013-01-08
2019-07-21
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
TRIPLE
Study Groups
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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
Placebo supplied as tablets
Vemurafenib
Vemurafenib supplied as tablets
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
Vemurafenib supplied as tablets
Cobimetinib
Cobimetinib supplied as tablets
Interventions
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Placebo
Placebo supplied as tablets
Vemurafenib
Vemurafenib supplied as tablets
Cobimetinib
Cobimetinib supplied as tablets
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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
18 Years
ALL
No
Sponsors
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Hoffmann-La Roche
INDUSTRY
Responsible Party
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Principal Investigators
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Clinical Trials
Role: STUDY_DIRECTOR
Hoffmann-La Roche
Locations
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University of Alabama at Birmingham
Birmingham, Alabama, United States
The Angeles Clinic and Research Institute - W LA Office
Los Angeles, California, United States
University of California Davis Health System
Sacramento, California, United States
Sutter Pacific Medical Foundation
Santa Rosa, California, United States
University Of Colorado
Aurora, Colorado, United States
Florida Cancer Specialists - Broadway
Fort Myers, Florida, United States
Mount Sinai Medical Center
Miami Beach, Florida, United States
Orlando Health Inc.
Orlando, Florida, United States
Northwestern Center For Clinical Research
Chicago, Illinois, United States
Uni of Kansas Medical Center; Dept of Neurology
Kansas City, Kansas, United States
U of L - Physicians Pulmonology; Dept of Neuroradiology and Dept of Diagnostic Radiology
Louisville, Kentucky, United States
Washington University School of Medicine; Dept of Medicine/Div of Medical Oncology
St Louis, Missouri, United States
Dartmouth-Hitchcock Medical Center; Department of Medicine
Lebanon, New Hampshire, United States
Novant Health Oncology Specialists
Winston-Salem, North Carolina, United States
University Hospitals of Cleveland
Cleveland, Ohio, United States
St. Luke's University Health network
Bethlehem, Pennsylvania, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States
University of Pittsburgh
Pittsburgh, Pennsylvania, United States
Rhode Island Hospital; Investigational Services
Providence, Rhode Island, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
Chris O'Brien Lifehouse
Camperdown, New South Wales, Australia
Lake Macquarie Private Hospital
Gateshead, New South Wales, Australia
Lismore Base Hospital; Cancer Care & Haematology Unit
Lismore, New South Wales, Australia
Melanoma Institute Australia
North Sydney, New South Wales, Australia
Princess Alexandra Hospital
Woolloongabba, New South Wales, Australia
Royal Darwin Hospital
Casuarina, Northern Territory, Australia
Greenslopes Private Hospital
Greenslopes, Queensland, Australia
Royal Brisbane and Women's Hospital
Herston, Queensland, Australia
Royal Adelaide Hospital; Hepatology
Adelaide, South Australia, Australia
Ashford Cancer Centre
Ashford SA, South Australia, Australia
Royal Hobart Hospital
Hobart, Tasmania, Australia
Launceston General Hospital; Gastroenterology Research
Launceston, Tasmania, Australia
Peninsula and South Eastern Haematology and Oncology Group
Frankston, Victoria, Australia
Austin Hospital
Heidelberg, Victoria, Australia
Peter MacCallum Cancer Centre-East Melbourne
Melbourne, Victoria, Australia
The Alfred Hospital
Prahan, Victoria, Australia
Fiona Stanley Hospital
Murdoch, Western Australia, Australia
Ordensklinikum Linz Elisabethinen
Linz, , Austria
Landesklinikum St. Pölten
Sankt Pölten, , Austria
Medizinische Universität Wien
Vienna, , Austria
Institut Jules Bordet; Department of Medical Oncology
Brussels, , Belgium
Cliniques Universitaires St-Luc
Brussels, , Belgium
UZ Antwerpen
Edegem, , Belgium
Jessa Zkh (Campus Virga Jesse)
Hasselt, , Belgium
CHU Sart-Tilman
Liège, , Belgium
AZ Delta (Campus Rumbeke)
Roeselare, , Belgium
BC Cancer Agency Vancouver Island Cancer Centre
Victoria, British Columbia, Canada
Juravinski Cancer Clinic; Department of Oncology
Hamilton, Ontario, Canada
The Ottawa Hospital Cancer Center; General Campus
Ottawa, Ontario, Canada
Toronto Sunnybrook Hospital
Toronto, Ontario, Canada
Princess Margaret Hospital; Department of Med Oncology
Toronto, Ontario, Canada
London Health Sciences Centre · Victoria Hospital;Department of Pediatrics
London, Quebec, Canada
McGill University Health Centre/Glen Site / Royal Victoria Hospital
Montreal, Quebec, Canada
Masarykuv onkologicky ustav
Brno, , Czechia
Fakultni nemocnice Hradec Kralove
Hradec Králové, , Czechia
Fakultní nemocnice Olomouc
Olomouc, , Czechia
Fakultni nemocnice Ostrava
Ostrava - Poruba, , Czechia
Multiscan s.r.o.
Pardubice, , Czechia
Fakultni nemocnice Kralovske Vinohrady
Prague, , Czechia
Vseobecna fakultni nemocnice v Praze
Prague, , Czechia
Fakultni nemocnice Motol; Neurologicka klinika
Prague, , Czechia
Nemocnice Na Bulovce
Prague, , Czechia
Groupe Hospitalier Saint André - Hôpital Saint André
Bordeaux, , France
Hôpital Ambroise Paré - Boulogne-Billancourt; Respiratory
Boulogne-Billancourt, , France
CHU Clermont Ferrand - Hôpital d'Estaing
Clermont-Ferrand, , France
CHU de Dijon - Hopital le Bocage
Dijon, , France
Centre Hospitalier Universitaire de Grenoble - Albert Michallon
La Tronche, , France
Hopital Claude Huriez - CHU Lille
Lille, , France
Hopital de la Timone
Marseille, , France
Hopital Saint Eloi
Montpellier, , France
CHU NANTES - Hôtel Dieu; Pharmacy
Nantes, , France
CHU Nice - Hopital de l'Archet 2
Nice, , France
Centre Hospitalier Lyon Sud
Pierre-Bénite, , France
Hopital Robert Debre; DERMATOLOGIE
Reims, , France
Centre Eugene Marquis; Service d'oncologie
Rennes, , France
St. Josef-Hospital; Studienambulanz
Bochum, , Germany
Elbekliniken Buxtehude GmbH
Buxtehude, , Germany
Universitaetsklinikum Koeln; Hematology/Oncology
Cologne, , Germany
Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden
Dresden, , Germany
Helios Klinikum Erfurt
Erfurt, , Germany
Universitätsklinikum Essen
Essen, , Germany
Universitaetsklinikum Freiburg
Freiburg im Breisgau, , Germany
SRH Wald-Klinikum Gera; Klinik für Hautkrankheiten und Allergologie
Gera, , Germany
Universitätsmedizin Göttingen
Göttingen, , Germany
Universitätsklinikum Hamburg-Eppendorf
Hamburg, , Germany
Medizinische Hochschule Hannover
Hanover, , Germany
Universitätsklinikum Heidelberg
Heidelberg, , Germany
Universitaetsklinikum Schleswig-Holstein - Campus Kiel; Klinik fuer Allgemeine Innere Medizin
Kiel, , Germany
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
Mainz, , Germany
Klinikum Mannheim GmbH Universitätsklinikum
Mannheim, , Germany
Klinikum der Ludwigs-Maximilians-Universitaet Muenchen
München, , Germany
Fachklinik Hornheide
Münster, , Germany
Universitaetsklinikum Regensburg
Regensburg, , Germany
Universitätsklinikum Tübingen
Tübingen, , Germany
Universitätsklinikum Wurzburg
Würzburg, , Germany
Orszagos Onkologiai Intezet
Budapest, , Hungary
Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaza
Gyula, , Hungary
Somogy Megyei Kaposi Mor Oktato Korhaz
Pécs, , Hungary
Szegedi Tud.Egyetem Szent-Gyorgyi Albert Klin.Kozp.
Szeged, , Hungary
Soroka Medical Center; Oncology Dept
Beersheba, , Israel
Rambam Health Care Campus
Haifa, , Israel
HADASSAH UNIVERSITY HOSPITAL, EIN KAREM; Oncology
Jerusalem, , Israel
Rabin Medical Center-Beilinson Campus;Hematology-Oncology
Petah Tikva, , Israel
Chaim Sheba Medical Center
Ramat Gan, , Israel
Tel Aviv Sourasky MC, Dana children's hospital;Oncology Division
Tel Aviv, , Israel
Istituto Tumori Giovanni Paolo II IRCSS; Ospedale Oncologico Bari
Bari, Apulia, Italy
Istituto Nazionale Tumori Fondazione G. Pascale
Napoli, Campania, Italy
Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori
Meldola, Emilia-Romagna, Italy
A.O.U. Policlinico di Modena
Modena, Emilia-Romagna, Italy
Istituto Nazionale Tumori Regina Elena IRCCS
Rome, Lazio, Italy
Istituto Nazionale per la Ricerca sul Cancro di Genova
Genoa, Liguria, Italy
Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)
Bergamo, Lombardy, Italy
Asst Degli Spedali Civili Di Brescia
Brescia, Lombardy, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, Lombardy, Italy
A.O.U. Senese Policlinico Santa Maria Alle Scotte
Siena, Tuscany, Italy
IOV - Istituto Oncologico Veneto IRCCS
Padua, Veneto, Italy
Amsterdam UMC Location VUMC
Amsterdam, , Netherlands
Leids Universitair Medisch Centrum; Cardiology
Leiden, , Netherlands
Maastricht University Medical Center
Maastricht, , Netherlands
Auckland City Hospital
Auckland, , New Zealand
Waikato Hospital
Hamilton, , New Zealand
Radiumhospitalet
Oslo, , Norway
TSBHI Altai Territorial oncological dispensary
Barnaul, , Russia
FSBSI "N. N. Blokhin Russian Cancer Research Center"
Moscow, , Russia
Moscow city oncology hospital #62 of Moscow Healthcare Department
Moscow, , Russia
BHI of Omsk region Clinical Oncology Dispensary
Omsk, , Russia
Pyatigorsky Oncologic Dispensary
Pyatigorsk, , Russia
Complexo Hospitalario Universitario de Santiago
Santiago de Compostela, LA Coruña, Spain
Clinica Universitaria de Navarra
Pamplona, Navarre, Spain
Hospital Universitario Virgen Macarena
Seville, Sevilla, Spain
Hospital Clínic i Provincial de Barcelona
Barcelona, , Spain
MD Anderson Cancer Center
Madrid, , Spain
Hospital Universitario 12 de Octubre
Madrid, , Spain
Hospital General Universitario de Valencia
Valencia, , Spain
Hospital Universitario Miguel Servet
Zaragoza, , Spain
Länssjukhuset Ryhov
Jönköping, , Sweden
Skånes Universitetssjukhus
Lund, , Sweden
Sahlgrenska Sjukhuset
Mölnlycke, , Sweden
Akademiska Sjukhuset
Uppsala, , Sweden
Inselspital-Universitaetsspital Bern
Bern, , Switzerland
Kantonsspital Graubuenden
Chur, , Switzerland
Bristol Haematology and Oncology Centre
Bristol, , United Kingdom
Addenbrooke's Hospital
Cambridge, , United Kingdom
Velindre Cancer Centre
Cardiff, , United Kingdom
Western General Hospital
Edinburgh, , United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, , United Kingdom
The Clatterbridge Cancer Centre NHS Foundation Trust
Liverpool, , United Kingdom
Barts and the London NHS Trust.
London, , United Kingdom
St George's Hospital; Courtyard Clinic
London, , United Kingdom
Royal Marsden Hospital - Fulham
London, , United Kingdom
Royal Marsden Hospital - London
London, , United Kingdom
Freeman Hospital
Newcastle upon Tyne, , United Kingdom
Nottingham University Hospitals; QMC Campus
Nottingham, , United Kingdom
Southampton General Hospital
Southampton, , United Kingdom
Royal Cornwall Hospital
Truro, , United Kingdom
New Cross Hospital
Wolverhampton, , United Kingdom
Countries
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References
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Barteselli G, Goodman GR, Patel Y, Caro I, Xue C, McCallum S. Characterization of Serous Retinopathy Associated with Cobimetinib: Integrated Safety Analysis of Four Studies. Drug Saf. 2022 Dec;45(12):1491-1499. doi: 10.1007/s40264-022-01248-2. Epub 2022 Oct 30.
Ascierto PA, Dreno B, Larkin J, Ribas A, Liszkay G, Maio M, Mandala M, Demidov L, Stroyakovskiy D, Thomas L, de la Cruz-Merino L, Atkinson V, Dutriaux C, Garbe C, Hsu J, Jones S, Li H, McKenna E, Voulgari A, McArthur GA. 5-Year Outcomes with Cobimetinib plus Vemurafenib in BRAFV600 Mutation-Positive Advanced Melanoma: Extended Follow-up of the coBRIM Study. Clin Cancer Res. 2021 Oct 1;27(19):5225-5235. doi: 10.1158/1078-0432.CCR-21-0809.
Ascierto PA, Ribas A, Larkin J, McArthur GA, Lewis KD, Hauschild A, Flaherty KT, McKenna E, Zhu Q, Mun Y, Dreno B. Impact of initial treatment and prognostic factors on postprogression survival in BRAF-mutated metastatic melanoma treated with dacarbazine or vemurafenib +/- cobimetinib: a pooled analysis of four clinical trials. J Transl Med. 2020 Aug 3;18(1):294. doi: 10.1186/s12967-020-02458-x.
de la Cruz-Merino L, Di Guardo L, Grob JJ, Venosa A, Larkin J, McArthur GA, Ribas A, Ascierto PA, Evans JTR, Gomez-Escobar A, Barteselli G, Eng S, Hsu JJ, Uyei A, Dreno B. Clinical features of serous retinopathy observed with cobimetinib in patients with BRAF-mutated melanoma treated in the randomized coBRIM study. J Transl Med. 2017 Jun 24;15(1):146. doi: 10.1186/s12967-017-1246-0.
Dreno B, Ribas A, Larkin J, Ascierto PA, Hauschild A, Thomas L, Grob JJ, Koralek DO, Rooney I, Hsu JJ, McKenna EF, McArthur GA. Incidence, course, and management of toxicities associated with cobimetinib in combination with vemurafenib in the coBRIM study. Ann Oncol. 2017 May 1;28(5):1137-1144. doi: 10.1093/annonc/mdx040.
Ascierto PA, McArthur GA, Dreno B, Atkinson V, Liszkay G, Di Giacomo AM, Mandala M, Demidov L, Stroyakovskiy D, Thomas L, de la Cruz-Merino L, Dutriaux C, Garbe C, Yan Y, Wongchenko M, Chang I, Hsu JJ, Koralek DO, Rooney I, Ribas A, Larkin J. Cobimetinib combined with vemurafenib in advanced BRAF(V600)-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial. Lancet Oncol. 2016 Sep;17(9):1248-60. doi: 10.1016/S1470-2045(16)30122-X. Epub 2016 Jul 30.
Larkin J, Ascierto PA, Dreno B, Atkinson V, Liszkay G, Maio M, Mandala M, Demidov L, Stroyakovskiy D, Thomas L, de la Cruz-Merino L, Dutriaux C, Garbe C, Sovak MA, Chang I, Choong N, Hack SP, McArthur GA, Ribas A. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med. 2014 Nov 13;371(20):1867-76. doi: 10.1056/NEJMoa1408868. Epub 2014 Sep 29.
Provided Documents
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Document Type: Study Protocol
Other Identifiers
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2012-003008-11
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
GO28141
Identifier Type: -
Identifier Source: org_study_id
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