A Study Comparing Vemurafenib Versus Vemurafenib Plus Cobimetinib in Participants With Metastatic Melanoma
- Conditions
- Malignant Melanoma
- Interventions
- Registration Number
- NCT01689519
- Lead Sponsor
- Hoffmann-La Roche
- 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 available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 495
- 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
-
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:
- All known CNS lesions have been treated with stereotactic therapy or surgery, AND
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo + Vemurafenib 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 + Vemurafenib Placebo 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. Cobimetinib + Vemurafenib 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. Cobimetinib + Vemurafenib Cobimetinib 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.
- Primary Outcome Measures
Name Time Method Progression-free Survival 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.
- Secondary Outcome Measures
Name Time Method Overall Survival 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 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 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.
Trial Locations
- Locations (156)
UZ Antwerpen
🇧🇪Edegem, Belgium
Velindre Cancer Centre
🇬🇧Cardiff, United Kingdom
Lismore Base Hospital; Cancer Care & Haematology Unit
🇦🇺Lismore, New South Wales, Australia
Chris O'Brien Lifehouse
🇦🇺Camperdown, New South Wales, Australia
Launceston General Hospital; Gastroenterology Research
🇦🇺Launceston, Tasmania, Australia
University Of Colorado
🇺🇸Aurora, Colorado, United States
Greenslopes Private Hospital
🇦🇺Greenslopes, Queensland, Australia
Fiona Stanley Hospital
🇦🇺Murdoch, Western Australia, Australia
Washington University School of Medicine; Dept of Medicine/Div of Medical Oncology
🇺🇸Saint Louis, Missouri, United States
Ashford Cancer Centre
🇦🇺Ashford SA, South Australia, Australia
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
🇩🇪Mainz, Germany
Sutter Pacific Medical Foundation
🇺🇸Santa Rosa, California, United States
Fachklinik Hornheide
🇩🇪Muenster, Germany
Vseobecna fakultni nemocnice v Praze
🇨🇿Praha 2, Czechia
Szegedi Tud.Egyetem Szent-Gyorgyi Albert Klin.Kozp.
🇭🇺Szeged, Hungary
Soroka Medical Center; Oncology Dept
🇮🇱Beer Sheva, Israel
Royal Brisbane and Women's Hospital
🇦🇺Herston, Queensland, Australia
Rhode Island Hospital; Investigational Services
🇺🇸Providence, Rhode Island, United States
Princess Alexandra Hospital
🇦🇺Woolloongabba, New South Wales, Australia
Juravinski Cancer Clinic; Department of Oncology
🇨🇦Hamilton, Ontario, Canada
Helios Klinikum Erfurt
🇩🇪Erfurt, Germany
Multiscan s.r.o.
🇨🇿Pardubice, Czechia
Fakultni nemocnice Hradec Kralove
🇨🇿Hradec Kralove, Czechia
Universitätsklinikum Essen
🇩🇪Essen, Germany
Nemocnice Na Bulovce
🇨🇿Prague, Czechia
Princess Margaret Hospital; Department of Med Oncology
🇨🇦Toronto, Ontario, Canada
Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden
🇩🇪Dresden, Germany
Groupe Hospitalier Saint André - Hôpital Saint André
🇫🇷Bordeaux, France
Fakultni nemocnice Ostrava
🇨🇿Ostrava - Poruba, Czechia
Universitätsmedizin Göttingen
🇩🇪Göttingen, Germany
Universitätsklinikum Heidelberg
🇩🇪Heidelberg, Germany
The Ottawa Hospital Cancer Center; General Campus
🇨🇦Ottawa, Ontario, Canada
Elbekliniken Buxtehude GmbH
🇩🇪Buxtehude, Germany
Hopital Claude Huriez - CHU Lille
🇫🇷Lille, France
Hopital Saint Eloi
🇫🇷Montpellier, France
Toronto Sunnybrook Hospital
🇨🇦Toronto, Ontario, Canada
CHU NANTES - Hôtel Dieu; Pharmacy
🇫🇷Nantes, France
Hopital Robert Debre; DERMATOLOGIE
🇫🇷Reims, France
Universitaetsklinikum Regensburg
🇩🇪Regensburg, Germany
Fakultni nemocnice Kralovske Vinohrady
🇨🇿Praha, Czechia
Masarykuv onkologicky ustav
🇨🇿Brno, Czechia
Orszagos Onkologiai Intezet
🇭🇺Budapest, Hungary
Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
Fakultní nemocnice Olomouc
🇨🇿Olomouc, Czechia
CHU de Dijon - Hopital le Bocage
🇫🇷Dijon, France
Hopital de la Timone
🇫🇷Marseille, France
CHU Nice - Hopital de l'Archet 2
🇫🇷Nice, France
Centre Eugene Marquis; Service d'oncologie
🇫🇷Rennes, France
SRH Wald-Klinikum Gera; Klinik für Hautkrankheiten und Allergologie
🇩🇪Gera, Germany
Universitaetsklinikum Schleswig-Holstein - Campus Kiel; Klinik fuer Allgemeine Innere Medizin
🇩🇪Kiel, Germany
Klinikum Mannheim GmbH Universitätsklinikum
🇩🇪Mannheim, Germany
Universitaetsklinikum Koeln; Hematology/Oncology
🇩🇪Koeln, Germany
Hospital Clínic i Provincial de Barcelona
🇪🇸Barcelona, Spain
Istituto Tumori Giovanni Paolo II IRCSS; Ospedale Oncologico Bari
🇮🇹Bari, Puglia, Italy
Moscow city oncology hospital #62 of Moscow Healthcare Department
🇷🇺Moscow, Russian Federation
McGill University Health Centre/Glen Site / Royal Victoria Hospital
🇨🇦Montréal, Quebec, Canada
Austin Hospital
🇦🇺Heidelberg, Victoria, Australia
TSBHI Altai Territorial oncological dispensary
🇷🇺Barnaul, Russian Federation
FSBSI "N. N. Blokhin Russian Cancer Research Center"
🇷🇺Moscow, Russian Federation
Uni of Kansas Medical Center; Dept of Neurology
🇺🇸Kansas City, Kansas, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
University Hospitals of Cleveland
🇺🇸Cleveland, Ohio, United States
University of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
The Angeles Clinic and Research Institute - W LA Office
🇺🇸Los Angeles, California, United States
Florida Cancer Specialists - Broadway
🇺🇸Fort Myers, Florida, United States
St. Luke's University Health network
🇺🇸Bethlehem, Pennsylvania, United States
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Lake Macquarie Private Hospital
🇦🇺Gateshead, New South Wales, Australia
Melanoma Institute Australia
🇦🇺North Sydney, New South Wales, Australia
Royal Adelaide Hospital; Hepatology
🇦🇺Adelaide, South Australia, Australia
Peninsula and South Eastern Haematology and Oncology Group
🇦🇺Frankston, Victoria, Australia
Ordensklinikum Linz Elisabethinen
🇦🇹Linz, Austria
CHU Sart-Tilman
🇧🇪Liège, Belgium
AZ Delta (Campus Rumbeke)
🇧🇪Roeselare, Belgium
CHU Clermont Ferrand - Hôpital d'Estaing
🇫🇷Clermont Ferrand cedex 1, France
St. Josef-Hospital; Studienambulanz
🇩🇪Bochum, Germany
Universitaetsklinikum Freiburg
🇩🇪Freiburg, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Universitätsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Universitätsklinikum Wurzburg
🇩🇪Würzburg, Germany
HADASSAH UNIVERSITY HOSPITAL, EIN KAREM; Oncology
🇮🇱Jerusalem, Israel
Rabin Medical Center-Beilinson Campus;Hematology-Oncology
🇮🇱Petach Tikva, Israel
Tel Aviv Sourasky MC, Dana children's hospital;Oncology Division
🇮🇱Tel Aviv, Israel
IOV - Istituto Oncologico Veneto IRCCS
🇮🇹Padova, Veneto, 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
Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)
🇮🇹Bergamo, Lombardia, Italy
Asst Degli Spedali Civili Di Brescia
🇮🇹Brescia, Lombardia, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milano, Lombardia, Italy
A.O.U. Senese Policlinico Santa Maria Alle Scotte
🇮🇹Siena, Toscana, Italy
Leids Universitair Medisch Centrum; Cardiology
🇳🇱Leiden, Netherlands
Auckland City Hospital
🇳🇿Auckland, New Zealand
Waikato Hospital
🇳🇿Hamilton, New Zealand
Radiumhospitalet
🇳🇴Oslo, Norway
BHI of Omsk region Clinical Oncology Dispensary
🇷🇺Omsk, Russian Federation
Hospital Universitario Virgen Macarena
🇪🇸Seville, Sevilla, Spain
Clinica Universitaria de Navarra
🇪🇸Pamplona, Navarra, Spain
MD Anderson Cancer Center
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital General Universitario de Valencia
🇪🇸Valencia, Spain
Länssjukhuset Ryhov
🇸🇪Jönköping, Sweden
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
Sahlgrenska Sjukhuset
🇸🇪Mölnlycke, Sweden
Akademiska Sjukhuset
🇸🇪Uppsala, Sweden
Kantonsspital Graubuenden
🇨🇭Chur, Switzerland
Bristol Haematology and Oncology Centre
🇬🇧Bristol, United Kingdom
Addenbrooke's Hospital
🇬🇧Cambridge, 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
Skånes Universitetssjukhus
🇸🇪Lund, Sweden
Hôpital Ambroise Paré - Boulogne-Billancourt; Respiratory
🇫🇷Boulogne Billancourt, France
Centre Hospitalier Universitaire de Grenoble - Albert Michallon
🇫🇷La Tronche, France
Centre Hospitalier Lyon Sud
🇫🇷Pierre Benite, France
Royal Cornwall Hospital
🇬🇧Truro, United Kingdom
New Cross Hospital
🇬🇧Wolverhampton, United Kingdom
Klinikum der Ludwigs-Maximilians-Universitaet Muenchen
🇩🇪München, Germany
Universitätsklinikum Tübingen
🇩🇪Tuebingen, Germany
Complexo Hospitalario Universitario de Santiago
🇪🇸Santiago de Compostela, LA Coruña, Spain
Fakultni nemocnice Motol; Neurologicka klinika
🇨🇿Praha, Czechia
University of California Davis Health System
🇺🇸Sacramento, California, United States
Northwestern Center For Clinical Research
🇺🇸Chicago, Illinois, United States
Orlando Health Inc.
🇺🇸Orlando, Florida, United States
Mount Sinai Medical Center
🇺🇸Miami Beach, Florida, United States
U of L - Physicians Pulmonology; Dept of Neuroradiology and Dept of Diagnostic Radiology
🇺🇸Louisville, Kentucky, United States
Novant Health Oncology Specialists
🇺🇸Winston-Salem, North Carolina, United States
Inselspital-Universitaetsspital Bern
🇨🇭Bern, Switzerland
Landesklinikum St. Pölten
🇦🇹St. Pölten, Austria
Medizinische Universität Wien
🇦🇹Wien, Austria
Institut Jules Bordet; Department of Medical Oncology
🇧🇪Bruxelles, Belgium
Cliniques Universitaires St-Luc
🇧🇪Bruxelles, Belgium
Jessa Zkh (Campus Virga Jesse)
🇧🇪Hasselt, Belgium
London Health Sciences Centre · Victoria Hospital;Department of Pediatrics
🇨🇦London, Quebec, Canada
Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaza
🇭🇺Gyula, Hungary
Somogy Megyei Kaposi Mor Oktato Korhaz
🇭🇺Pecs, Hungary
Rambam Health Care Campus
🇮🇱Haifa, Israel
Dartmouth-Hitchcock Medical Center; Department of Medicine
🇺🇸Lebanon, New Hampshire, United States
BC Cancer Agency Vancouver Island Cancer Centre
🇨🇦Victoria, British Columbia, Canada
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Istituto Nazionale Tumori Regina Elena IRCCS
🇮🇹Roma, Lazio, Italy
Amsterdam UMC Location VUMC
🇳🇱Amsterdam, Netherlands
Maastricht University Medical Center
🇳🇱Maastricht, Netherlands
Pyatigorsky Oncologic Dispensary
🇷🇺Pyatigorsk, Russian Federation
Istituto Nazionale per la Ricerca sul Cancro di Genova
🇮🇹Genova, Liguria, Italy
The Alfred Hospital
🇦🇺Prahan, Victoria, Australia
Peter MacCallum Cancer Centre-East Melbourne
🇦🇺Melbourne, Victoria, Australia
Royal Hobart Hospital
🇦🇺Hobart, Tasmania, Australia
Royal Darwin Hospital
🇦🇺Casuarina, Northern Territory, Australia