A Study of Vemurafenib Adjuvant Therapy in Participants With Surgically Resected Cutaneous BRAF-Mutant Melanoma

Melanoma Clinical Trial

— BRIM8  

Official title:

A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Vemurafenib (RO5185426) Adjuvant Therapy in Patients With Surgically Resected, Cutaneous BRAF-Mutant Melanoma at High Risk for Recurrence

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01667419
• Other study ID #: GO27826
• Secondary ID: 2011-004011-24
• Status: Completed
• Phase: Phase 3
• Start date: September 24, 2012
• Est. completion date: July 13, 2018

Study information

• Verified date: July 2019
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This multicenter, randomized, double-blind, placebo-controlled study will evaluate the efficacy and safety of vemurafenib in participants with completely resected, cutaneous BRAF mutation-positive melanoma at high risk for recurrence. Participants will be enrolled in two separate cohorts: Cohort 1 will include participants with completely resected Stage IIC, IIIA (participants with one or more nodal metastasis greater than [>] 1 millimeter [mm] in diameter), or IIIB cutaneous melanoma, as defined by the American Joint Committee on Cancer (AJCC) Classification, Version 7; Cohort 2 will include participants with Stage IIIC cutaneous melanoma, as defined by this classification scheme. Within each cohort, participants will be randomized (1:1 ratio) to receive vemurafenib or matching placebo over a 52-week period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 498
• Est. completion date: July 13, 2018
• Est. primary completion date: June 23, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed melanoma of cutaneous origin

• Participants with BRAFV600 mutation-positive, cutaneous melanoma (either pathologic Stage IIC or Stage III according to AJCC Staging Criteria version 7 that has been completely resected

• BRAF V600 mutation status of the current primary tumor or involved lymph node determined to be positive using the cobas BRAF V600 mutation test

• Surgically rendered free of disease within 90 days of randomization

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Life expectancy of at least 5 years

• Fully recovered from the effects of any major surgery or significant traumatic injury prior to the first dose of study treatment

• Adequate hematologic, hepatic, and renal function

Exclusion Criteria:

• History of any systemic or local therapy (e.g., chemotherapy, biologic or targeted therapy, hormonal therapy, or photodynamic therapy) for the treatment or prevention of melanoma, including interferon alpha-2b and pegylated interferon alpha-2b

• History of limb perfusion therapy

• History of radiotherapy for the treatment of melanoma

• Invasive malignancy other than melanoma at the time of enrollment or within 5 years prior to first dose of study treatment

• Family history of inherited colon cancer syndromes

• Known personal history of >3 adenomatous colorectal polyps or a personal history of adenomatous colorectal polyp(s) >2 centimeters (cm) in size

• History of or current clinical, radiographic, or pathologic evidence of in-transit metastases, satellite, or microsatellite lesions

• History of or current clinical, radiographic, or pathologic evidence of recurrent lymph node involvement after resection of a primary melanoma with lymph node involvement at any time in the past

• History of local and/or regional and/or distant melanoma recurrence

• History or current radiographic or pathologic evidence of distant metastases

• History of clinically significant cardiac or pulmonary dysfunction

• Major surgical procedure or significant traumatic injury within 4 weeks prior to first dose of study treatment

• Infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C virus

Related Conditions & MeSH terms

• Melanoma

Intervention

Drug:
• Vemurafenib
4 tablets of vemurafenib 240 mg each (total 960 mg) were administered orally as per the schedule specified in the respective arm.
• Placebo
Placebo matching to vemurafenib were administered orally as per the schedule specified in the respective arm.

Locations

Country	Name	City	State
Argentina	Fundación CIDEA	Buenos Aires
Argentina	Hospital Britanico de Buenos Aires	Ciudad Autonoma Buenos Aires
Argentina	Instituto Medico Especializado Alexander Fleming	Ciudad Autonoma Buenos Aires
Argentina	Hospital Universitario Austral	Derqui-Pilar
Argentina	Centro de Investigacion Pergamino SA	Pergamino
Argentina	Instituto de Oncología de Rosario	Rosario
Argentina	ISIS Clinica Especializada	Santa Fe
Australia	Royal Adelaide Hospital; Hepatology	Adelaide	South Australia
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	Cairns Base Hospital	Cairns	Queensland
Australia	Chris O'Brien Lifehouse	Camperdown	New South Wales
Australia	Peninsula Oncology Centre; Frankston Private	Frankston	Victoria
Australia	Launceston General Hospital; Gastroenterology Research	Launceston	Tasmania
Australia	Alfred Hospital	Melbourne	Victoria
Australia	Peter Maccallum Cancer Centre	Melbourne	Victoria
Australia	Fiona Stanley Hospital	Murdoch	Western Australia
Australia	Melanoma Institute Australia	North Sydney	New South Wales
Australia	The Townsville Hospital; Townsville Cancer Centre	Townsville	Queensland
Australia	Calvary Mater Newcastle	Waratah	New South Wales
Australia	Border Medical Oncology	Wodonga	New South Wales
Australia	Southern Medical Day Care Centre	Wollongong	New South Wales
Australia	Queen Elizabeth Hospital	Woodville	South Australia
Austria	Medizinische Universität Innsbruck	Innsbruck
Austria	Klinikum Wels-Grieskirchen	Wels
Austria	Krankenanstalt Rudolfstiftung Wien	Wien
Austria	Medizinische Universität Wien	Wien
Belgium	ZNA Middelheim	Antwerpen
Belgium	Institut Jules Bordet	Brussels
Belgium	UZ Antwerpen	Edegem
Belgium	UZ Gent	Gent
Belgium	Jessa Zkh (Campus Virga Jesse)	Hasselt
Belgium	AZ Groeninge, Apotheek	Kortrijk
Brazil	Trymed Clinical Research	Belo Horizonte	MG
Brazil	Hospital de Caridade de Ijuí	Ijuí	RO
Brazil	CITO - Centro Integrado de Terapia Onco-Hematológica - Hospital da Cidade de Passo Fundo	Passo Fundo	RS
Brazil	Clinica de Oncologia de Porto Alegre - CliniOnco	Porto Alegre	RS
Brazil	Hospital das Clinicas - UFRGS	Porto Alegre	RS
Brazil	Hospital Sírio-Libanês	Sao Paulo	SP
Canada	LHSC - Victoria Hospital; Department of Pediatrics	London	Ontario
Canada	CHUM Hôpital Notre-Dame	Montreal	Quebec
Canada	Mcgill University - Royal Victoria Hospital; Oncology	Montreal	Quebec
Canada	The Ottawa Hospital Cancer Center; General Campus	Ottawa	Ontario
Canada	Saint John Regional Hospital; Department of Oncology	Saint John	New Brunswick
Canada	CHUQ - Hôtel-Dieu de Québec	Ste-Foy	Quebec
Canada	Princess Margaret Hospital; Department of Med Oncology	Toronto	Ontario
Canada	Toronto Sunnybrook Hospital	Toronto	Ontario
Canada	BC Cancer Agency Vancouver Centre - PARENT; BC Cancer Agency	Vancouver	British Columbia
Canada	Saint Boniface General Hospital; Section of Nephrology BG 007	Winnipeg	Manitoba
Croatia	General Hospital Pula	Pula
Croatia	General Hospital Varazdin	Varazdin
Croatia	Clinical Hospital Center Sestre Milosrdnice	Zagreb
Croatia	Clinical Hospital Centre Zagreb	Zagreb
Czechia	Masarykuv onkologicky ustav	Brno
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Kralove
Czechia	Fakultní nemocnice Olomouc	Olomouc
Czechia	Fakultni nemocnice Ostrava	Ostrava - Poruba
Czechia	Nemocnice Na Bulovce	Prague
Czechia	Fakultni nemocnice Kralovske Vinohrady	Praha
Czechia	Vseobecna fakultni nemocnice v Praze	Praha 2
Estonia	East Tallinn Central Hospital; Clinic of Internal Medicine	Tallinn
Estonia	North Estonia Medical Centre Foundation	Tallinn
Estonia	Tartu University Hospital; Clinic of Hematology and Oncology	Tartu
France	CHU Besançon - Hôpital Jean Minjoz	Besançon Cedex
France	Groupe Hospitalier Saint André - Hôpital Saint André	Bordeaux
France	Hôpital Ambroise Paré - Boulogne-Billancourt; Respiratory	Boulogne Billancourt
France	Hopital Claude Huriez - CHU Lille	Lille
France	Hopital de la Timone	Marseille
France	CHU NANTES - Hôtel Dieu; Pharmacy	Nantes
France	CHU Nice - Hopital de l'Archet 2	Nice
France	Hôpital Saint-Louis	Paris
France	Centre Hospitalier Lyon Sud	Pierre Benite
France	CHU de Rouen Hopital; Service de Neurologie	Rouen
France	CHU de Toulouse - Hôpital Larrey	Toulouse
Germany	St. Josef-Hospital Universitaetsklinikum	Bochum
Germany	Elbekliniken Buxtehude GmbH	Buxtehude
Germany	Universitätsklinikum Essen	Essen
Germany	Universitaetsklinikum Frankfurt	Frankfurt
Germany	Universitätsklinikum Heidelberg	Heidelberg
Germany	Universitaetsklinikum Schleswig-Holstein - Campus Kiel; Klinik fuer Allgemeine Innere Medizin	Kiel
Germany	Universitätsklinikum Koeln	Koeln
Germany	Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz; Apotheke	Mainz
Germany	Klinikum Mannheim GmbH Universitätsklinikum	Mannheim
Germany	Fachklinik Hornheide	Muenster
Germany	Universitätsklinikum Tübingen	Tuebingen
Germany	Universitätsklinikum Wurzburg	Würzburg
Ireland	Cork University Hospital	Cork
Ireland	Mater Private Hospital	Dublin
Ireland	The Mater Misericordiae Hospital	Dublin
Ireland	University College Hospital	Galway
Israel	Soroka Medical Center	Beer Sheva
Israel	Rambam Health Care Campus	Haifa
Israel	Hadassah University Hospital - Ein Kerem	Jerusalem
Israel	Rabin Medical Center-Beilinson Campus	Petach Tikva
Israel	Chaim Sheba Medical Center	Ramat Gan
Israel	Tel-Aviv Sourasky Medical Center	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 Europeo Di Oncologia	Milano	Lombardia
Italy	Ospedale San Raffaele	Milano	Lombardia
Italy	Istituto Nazionale Tumori Fondazione G. Pascale	Napoli	Campania
Italy	IOV - Istituto Oncologico Veneto IRCCS	Padova	Veneto
Italy	Azienda Ospedaliera Universitaria Policlinico Tor Vergata	Roma	Lazio
Italy	IDI-Istituto Dermopatico dell'Immacolata IRCCS	Roma	Lazio
Italy	Istituto Nazionale Tumori Regina Elena IRCCS	Roma	Lazio
Italy	IRCCS Istituto Clinico Humanitas; Farmacia	Rozzano	Lombardia
Italy	A.O.U. Senese Policlinico Santa Maria Alle Scotte	Siena	Toscana
Mexico	Centro Oncologico Belenus	Cuernavaca
Mexico	Hospital Civil de Guadalajara Fray Antonio Alcalde	Guadalajara
Mexico	Centro Regiomontano de Investigación Clínica	Monterrey
Mexico	Sanatorio la Luz	Morelia
Netherlands	Universitair Medisch Centrum Groningen	Groningen
Netherlands	Leids Universitair Medisch Centrum; Cardiology	Leiden
New Zealand	Christchurch Hospital NZ	Christchurch
New Zealand	Wellington Hospital	Wellington
Norway	Stavanger Universitetssykehus, Helse Stavanger HF	Stavanger
Poland	SPZOZ MSW zWarminsko-MazurskimCen.Onko.wOlsztynie	Olsztyn
Poland	Przychodnia Med-Polonia Sp. z o.o.	Poznan
Poland	Centrum Onkologii- Instytut; im. M.Sklodowskiej-Curie	Warszawa
Poland	Dolnoslaskie Centrum Onkologii	Wroclaw
Portugal	IPO de Coimbra; Servico de Oncologia Medica	Coimbra
Portugal	Hospital do Espirito Santo; Servico de Oncologia Medica	Evora
Portugal	Hospital de Santa Maria; Servico de Oncologia Medica	Lisboa
Portugal	IPO do Porto; Servico de Oncologia Medica	Porto
Russian Federation	Krasnodar City Oncology Center	Krasnodar
Russian Federation	Moscow City Oncology Hospital #62	Moscovskaya Oblast	Moskovskaja Oblast
Russian Federation	FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"	Moscow
Russian Federation	Scientific Research Oncology Institute named after N.N. Petrov	St. Petersburg
Serbia	Clinical Center Bezanijska Kosa	Belgrade
Serbia	Institute of Oncology and Radiology of Serbia	Belgrade
Serbia	Military Medical Academy	Belgrade
Serbia	Institute for oncology of Vojvodina	Sremska Kamenica
South Africa	GVI Rondebosch Oncology Centre	Cape Town
South Africa	Mary Potter Oncology Centre	Groenkloof
South Africa	Groote Schuur Hospital Radiation Oncology Department; Department of Radiation Oncology	Observatory
South Africa	University of Pretoria Oncology Department	Pretoria
South Africa	Sandton Oncology Medical Group	Sandton
Spain	Hospital de la Santa Creu; i Sant Pau	Barcelona
Spain	Institut Catala d Oncologia Hospital Duran i Reynals	Barcelona
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Costa del Sol; Servicio de Oncologia	Marbella	Malaga
Spain	Hospital Clinico Universitario de Santiago	Santiago de Compostela	LA Coruña
Spain	Hospital Universitari i Politecnic La Fe	Valencia
Sweden	Länssjukhuset Ryhov	Jönköping
Sweden	Norrlands Universitetssjukhus	Umea
Sweden	Centrallasarettet Växjö	Växjö
Switzerland	CHUV; Departement d'Oncologie	Lausanne
Ukraine	CI Dnipropetrovsk CMCH 4 of Dnipropetrovsk RC Dept of Chemotherapy SI Dnipropetrovsk MA of MOHU	Dnipropetrovsk
Ukraine	Lviv State Oncological Regional Treatment and Diagnostic Center	Lviv
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	Queen Elizabeth Hospital	Kings Lynn
United Kingdom	Guys and St Thomas NHS Foundation Trust, Guys Hospital	London
United Kingdom	Nottingham University Hospitals City Campus	Nottingham
United Kingdom	Churchill Hospital	Oxford
United Kingdom	Royal Cornwall Hospital	Truro
United Kingdom	New Cross Hospital	Wolverhampton
United States	University Of Colorado	Aurora	Colorado
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	UCLA Department of Medicine; Division of Hematology / Oncology	California City	California
United States	MUSC Hollings Cancer Center/cannon Park Place; Attn: Tamara Saunders	Charleston	South Carolina
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Duke University Medical Center; Oncology	Durham	North Carolina
United States	Florida Cancer Specialists - Broadway	Fort Myers	Florida
United States	West Clinic	Germantown	Tennessee
United States	Indiana University Health; Goshen Center for Cancer Care	Goshen	Indiana
United States	St. Mary's Hospital Regional Cancer Center	Grand Junction	Colorado
United States	Kaiser Permanente - Hayward	Hayward	California
United States	Memorial Healthcare System	Hollywood	Florida
United States	MD Anderson Cancer Center	Houston	Texas
United States	Indiana University Department of Medicine; Division of Infectious Diseases	Indianapolis	Indiana
United States	UCLA Hematology Oncology - Irvine	Irvine	California
United States	St. Luke's Hospital	Kansas City	Missouri
United States	University of Kansas Medical Center; Cancer Center	Kansas City	Missouri
United States	UCSD Moores Cancer Center	La Jolla	California
United States	Cancer Center Of Santa Barbara; Network Clinical Research Specialist	Los Angeles	California
United States	The Angeles Clinic and Research Institute - W LA Office	Los Angeles	California
United States	TRIO-US Network Administration; Network Clinical Research Specialist	Los Angeles	California
United States	U of L - Physicians Pulmonology; Dept of Neuroradiology and Dept of Diagnostic Radiology	Louisville	Kentucky
United States	Mary Babb Randolph Cancer Center	Morgantown	West Virginia
United States	Tennessee Oncology PLLC - Nashville (20th Ave)	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	New York University Medical Center PRIME; NYU Clinical Cancer Center	New York	New York
United States	Kaiser Foundation Hospital - Oakland (W. MacArthur)	Oakland	California
United States	Kaiser Permanente - Oakland	Oakland	California
United States	Oncology Specialists, S.C.	Park Ridge	Illinois
United States	UCLA Healthcare/Pasadena Oncology	Pasadena	California
United States	University of Pennsylvania Health System	Philadelphia	Pennsylvania
United States	Atlantic Health Systems; Pediatrics	Randolph	New Jersey
United States	Kaiser Permanente - Roseville	Roseville	California
United States	Kaiser Permanente Sacramento Medical Center	Sacramento	California
United States	Washington University; Dept of Medicine/Div of Medical Oncology	Saint Louis	Missouri
United States	Kaiser Permanente	San Francisco	California
United States	K. Permanente - San Jose	San Jose	California
United States	Coastal Integrative Cancer Care	San Luis Obispo	California
United States	Kaiser Permanente - Santa Clara	Santa Clara	California
United States	GulfCoast Oncology	Sarasota	Florida
United States	Kaiser Permanente - South San Francisco	South San Francisco	California
United States	Stanford University School of Medicine; Stanford Hospital Pharmacy	Stanford	California
United States	UCLA Cancer Center Hema/Oncol	Valencia	California
United States	Kaiser Permanente - Vallejo	Vallejo	California
United States	Kaiser Permanente - Walnut Creek	Walnut Creek	California
United States	UCLA Hematology Oncology - Westlake	Westlake Village	California

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Croatia,  Czechia,  Estonia,  France,  Germany,  Ireland,  Israel,  Italy,  Mexico,  Netherlands,  New Zealand,  Norway,  Poland,  Portugal,  Russian Federation,  Serbia,  South Africa,  Spain,  Sweden,  Switzerland,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-Free Survival (DFS) as Assessed Using Contrast-Enhanced Magnetic Resonance Imaging (MRI) or Contrast Enhanced Computed Tomography (CT)	DFS was defined as the time from randomization until the date of the first local, regional, or distant melanoma recurrence, occurrence of new primary melanoma, or death from any cause.	From randomization until the date of the first local, regional, or distant melanoma recurrence, occurrence of new primary melanoma, or death from any cause (up to the April 17, 2017 data cut-off, approximately 4.5 years)
Secondary	Distant Metastasis-Free Survival (DMFS) as Assessed Using Contrast-Enhanced MRI or Contrast Enhanced CT	DMFS was defined as the time from randomization until the date of diagnosis of distant (i.e. non-locoregional) metastases or death from any cause.	From randomization until the date of diagnosis of distant (i.e., non-locoregional) metastases or death from any cause (up to the April 17, 2017 data cut-off, approximately 4.5 years)
Secondary	Overall Survival (OS)	OS is defined as the time from randomization until the date of death from any cause.	From randomization until the date of death from any cause (up until 13-July-2018, approximately 6 years)
Secondary	Percentage of Participants With Adverse Events	An adverse event is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution.	From randomization up to study completion or discontinuation (up until 13-July-2018, approximately 6 years)
Secondary	Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Score	European Organisation for Research and Treatment of Cancer 30-Item Quality of Life Questionnaire assesses 8 symptoms, function, financial difficulties, and a global health status/health-related quality of life (HRQoL). Most questions use a 4-point scale (1 'Not at all' to 4 'Very much';2 questions use a 7-point scale (1 'very poor' to 7 'Excellent'). Scores were averaged and transformed to a 0-100 scale. Higher scores for the function and HRQoL represent higher levels of functioning and HRQoL, higher scores for the symptom represent higher levels of symptoms/problems, higher score for financial difficulty represent higher level of perceived financial burden of treatment. Changes of 5-10 points are considered to represent a minimally important difference to participants. A positive value means an increase, and negative value means a decrease in score at the indicated time-point relative to the score at baseline (Cycle 1 Day 1).	Day 1, Day 8, Day 15, Day 22 of Cycle 1;Day 1, Day 15 of Cycle 2;Day 1 Cycles 3-13;end of treatment(up to 13 months);every 13 weeks thereafter until recurrence or occurrence of a new primary melanoma (up to 17-Apr-17 data cut-off,approximately 4.5 years)
Secondary	Plasma Concentration of Vemurafenib		Pre-morning dose (0 hour [hr]) and 1 to 4 hrs post-dose on Days 1, 8, 15, and 22 of Cycle 1; pre-morning dose (0 hr) on Days 1 and 15 of Cycle 2; pre-morning dose (0 hr) on Day 1 of Cycles 3-13; at end of treatment (up to 13 months)