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

Malignant Melanoma Clinical Trial

— coBRIM  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01689519
• Other study ID #: GO28141
• Secondary ID: 2012-003008-11
• Status: Completed
• Phase: Phase 3
• Start date: January 8, 2013
• Est. completion date: July 21, 2019

Study information

• Verified date: April 2022
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 495
• Est. completion date: July 21, 2019
• Est. primary completion date: May 9, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Malignant Melanoma
• Melanoma

Intervention

Drug:
• Placebo
Placebo supplied as tablets
• Vemurafenib
Vemurafenib supplied as tablets
• Cobimetinib
Cobimetinib supplied as tablets

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital; Hepatology	Adelaide	South Australia
Australia	Ashford Cancer Centre	Ashford SA	South Australia
Australia	Chris O'Brien Lifehouse	Camperdown	New South Wales
Australia	Royal Darwin Hospital	Casuarina	Northern Territory
Australia	Peninsula and South Eastern Haematology and Oncology Group	Frankston	Victoria
Australia	Lake Macquarie Private Hospital	Gateshead	New South Wales
Australia	Greenslopes Private Hospital	Greenslopes	Queensland
Australia	Austin Hospital	Heidelberg	Victoria
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	Launceston General Hospital; Gastroenterology Research	Launceston	Tasmania
Australia	Lismore Base Hospital; Cancer Care & Haematology Unit	Lismore	New South Wales
Australia	Peter MacCallum Cancer Centre-East Melbourne	Melbourne	Victoria
Australia	Fiona Stanley Hospital	Murdoch	Western Australia
Australia	Melanoma Institute Australia	North Sydney	New South Wales
Australia	The Alfred Hospital	Prahan	Victoria
Australia	Princess Alexandra Hospital	Woolloongabba	New South Wales
Austria	Ordensklinikum Linz Elisabethinen	Linz
Austria	Landesklinikum St. Pölten	St. Pölten
Austria	Medizinische Universität Wien	Wien
Belgium	Cliniques Universitaires St-Luc	Bruxelles
Belgium	Institut Jules Bordet; Department of Medical Oncology	Bruxelles
Belgium	UZ Antwerpen	Edegem
Belgium	Jessa Zkh (Campus Virga Jesse)	Hasselt
Belgium	CHU Sart-Tilman	Liège
Belgium	AZ Delta (Campus Rumbeke)	Roeselare
Canada	Juravinski Cancer Clinic; Department of Oncology	Hamilton	Ontario
Canada	London Health Sciences Centre · Victoria Hospital;Department of Pediatrics	London	Quebec
Canada	McGill University Health Centre/Glen Site / Royal Victoria Hospital	Montréal	Quebec
Canada	The Ottawa Hospital Cancer Center; General Campus	Ottawa	Ontario
Canada	Princess Margaret Hospital; Department of Med Oncology	Toronto	Ontario
Canada	Toronto Sunnybrook Hospital	Toronto	Ontario
Canada	BC Cancer Agency Vancouver Island Cancer Centre	Victoria	British Columbia
Czechia	Masarykuv onkologicky ustav	Brno
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Kralove
Czechia	Fakultní nemocnice Olomouc	Olomouc
Czechia	Fakultni nemocnice Ostrava	Ostrava - Poruba
Czechia	Multiscan s.r.o.	Pardubice
Czechia	Nemocnice Na Bulovce	Prague
Czechia	Fakultni nemocnice Kralovske Vinohrady	Praha
Czechia	Fakultni nemocnice Motol; Neurologicka klinika	Praha
Czechia	Vseobecna fakultni nemocnice v Praze	Praha 2
France	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 cedex 1
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 Benite
France	Hopital Robert Debre; DERMATOLOGIE	Reims
France	Centre Eugene Marquis; Service d'oncologie	Rennes
Germany	St. Josef-Hospital; Studienambulanz	Bochum
Germany	Elbekliniken Buxtehude GmbH	Buxtehude
Germany	Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden	Dresden
Germany	Helios Klinikum Erfurt	Erfurt
Germany	Universitätsklinikum Essen	Essen
Germany	Universitaetsklinikum Freiburg	Freiburg
Germany	SRH Wald-Klinikum Gera; Klinik für Hautkrankheiten und Allergologie	Gera
Germany	Universitätsmedizin Göttingen	Göttingen
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitätsklinikum Heidelberg	Heidelberg
Germany	Universitaetsklinikum Schleswig-Holstein - Campus Kiel; Klinik fuer Allgemeine Innere Medizin	Kiel
Germany	Universitaetsklinikum Koeln; Hematology/Oncology	Koeln
Germany	Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz	Mainz
Germany	Klinikum Mannheim GmbH Universitätsklinikum	Mannheim
Germany	Fachklinik Hornheide	Muenster
Germany	Klinikum der Ludwigs-Maximilians-Universitaet Muenchen	München
Germany	Universitaetsklinikum Regensburg	Regensburg
Germany	Universitätsklinikum Tübingen	Tuebingen
Germany	Universitätsklinikum Wurzburg	Würzburg
Hungary	Orszagos Onkologiai Intezet	Budapest
Hungary	Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaza	Gyula
Hungary	Somogy Megyei Kaposi Mor Oktato Korhaz	Pecs
Hungary	Szegedi Tud.Egyetem Szent-Gyorgyi Albert Klin.Kozp.	Szeged
Israel	Soroka Medical Center; Oncology Dept	Beer Sheva
Israel	Rambam Health Care Campus	Haifa
Israel	HADASSAH UNIVERSITY HOSPITAL, EIN KAREM; Oncology	Jerusalem
Israel	Rabin Medical Center-Beilinson Campus;Hematology-Oncology	Petach Tikva
Israel	Chaim Sheba Medical Center	Ramat Gan
Israel	Tel Aviv Sourasky MC, Dana children's hospital;Oncology Division	Tel Aviv
Italy	Istituto Tumori Giovanni Paolo II IRCSS; Ospedale Oncologico Bari	Bari	Puglia
Italy	Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)	Bergamo	Lombardia
Italy	Asst Degli Spedali Civili Di Brescia	Brescia	Lombardia
Italy	Istituto Nazionale per la Ricerca sul Cancro di Genova	Genova	Liguria
Italy	Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori	Meldola	Emilia-Romagna
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano	Lombardia
Italy	A.O.U. Policlinico di Modena	Modena	Emilia-Romagna
Italy	Istituto Nazionale Tumori Fondazione G. Pascale	Napoli	Campania
Italy	IOV - Istituto Oncologico Veneto IRCCS	Padova	Veneto
Italy	Istituto Nazionale Tumori Regina Elena IRCCS	Roma	Lazio
Italy	A.O.U. Senese Policlinico Santa Maria Alle Scotte	Siena	Toscana
Netherlands	Amsterdam UMC Location VUMC	Amsterdam
Netherlands	Leids Universitair Medisch Centrum; Cardiology	Leiden
Netherlands	Maastricht University Medical Center	Maastricht
New Zealand	Auckland City Hospital	Auckland
New Zealand	Waikato Hospital	Hamilton
Norway	Radiumhospitalet	Oslo
Russian Federation	TSBHI Altai Territorial oncological dispensary	Barnaul
Russian Federation	FSBSI "N. N. Blokhin Russian Cancer Research Center"	Moscow
Russian Federation	Moscow city oncology hospital #62 of Moscow Healthcare Department	Moscow
Russian Federation	BHI of Omsk region Clinical Oncology Dispensary	Omsk
Russian Federation	Pyatigorsky Oncologic Dispensary	Pyatigorsk
Spain	Hospital Clínic i Provincial de Barcelona	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	MD Anderson Cancer Center	Madrid
Spain	Clinica Universitaria de Navarra	Pamplona	Navarra
Spain	Complexo Hospitalario Universitario de Santiago	Santiago de Compostela	LA Coruña
Spain	Hospital Universitario Virgen Macarena	Seville	Sevilla
Spain	Hospital General Universitario de Valencia	Valencia
Spain	Hospital Universitario Miguel Servet	Zaragoza
Sweden	Länssjukhuset Ryhov	Jönköping
Sweden	Skånes Universitetssjukhus	Lund
Sweden	Sahlgrenska Sjukhuset	Mölnlycke
Sweden	Akademiska Sjukhuset	Uppsala
Switzerland	Inselspital-Universitaetsspital Bern	Bern
Switzerland	Kantonsspital Graubuenden	Chur
United Kingdom	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	Royal Marsden Hospital - Fulham	London
United Kingdom	Royal Marsden Hospital - London	London
United Kingdom	St George's Hospital; Courtyard Clinic	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 States	University Of Colorado	Aurora	Colorado
United States	St. Luke's University Health network	Bethlehem	Pennsylvania
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Northwestern Center For Clinical Research	Chicago	Illinois
United States	University Hospitals of Cleveland	Cleveland	Ohio
United States	Florida Cancer Specialists - Broadway	Fort Myers	Florida
United States	Uni of Kansas Medical Center; Dept of Neurology	Kansas City	Kansas
United States	Dartmouth-Hitchcock Medical Center; Department of Medicine	Lebanon	New Hampshire
United States	The Angeles Clinic and Research Institute - W LA Office	Los Angeles	California
United States	U of L - Physicians Pulmonology; Dept of Neuroradiology and Dept of Diagnostic Radiology	Louisville	Kentucky
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Orlando Health Inc.	Orlando	Florida
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	University of California Davis Health System	Sacramento	California
United States	Washington University School of Medicine; Dept of Medicine/Div of Medical Oncology	Saint Louis	Missouri
United States	Sutter Pacific Medical Foundation	Santa Rosa	California
United States	Novant Health Oncology Specialists	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Czechia,  France,  Germany,  Hungary,  Israel,  Italy,  Netherlands,  New Zealand,  Norway,  Russian Federation,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival	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	Overall Survival	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)
Secondary	Percentage of Participants With an Objective Response	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)
Secondary	Duration of Response	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)