A Study of Vemurafenib Adjuvant Therapy in Participants With Surgically Resected Cutaneous BRAF-Mutant Melanoma (BRIM8)

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

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.

Study Overview

• Status: Completed
• Conditions: Melanoma
• Intervention / Treatment: Drug: Vemurafenib; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 498
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1425DTG
    • Fundacion Cidea
  • Ciudad Autonoma Buenos Aires, Argentina, C1284AEB
    • Hospital Britanico de Buenos Aires
  • Ciudad Autonoma Buenos Aires, Argentina, 1426
    • Instituto Médico Especializado Alexander Fleming
  • Derqui-Pilar, Argentina, B1629ODT
    • Hospital Universitario Austral
  • Pergamino, Argentina, B2700CPM
    • Centro de Investigacion Pergamino SA
  • Rosario, Argentina, S2000KZE
    • Instituto de Oncología de Rosario
  • Santa Fe, Argentina, S3000
    • ISIS Clinica Especializada
• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Chris O'Brien Lifehouse
    • North Sydney, New South Wales, Australia, 2060
      • Melanoma Institute Australia
    • Waratah, New South Wales, Australia, 2298
      • Calvary Mater Newcastle
    • Wodonga, New South Wales, Australia, 3690
      • Border Medical Oncology
    • Wollongong, New South Wales, Australia, 2500
      • Southern Medical Day Care Centre
  • Queensland
    • Cairns, Queensland, Australia, 4870
      • Cairns Base Hospital
    • Townsville, Queensland, Australia, 4812
      • The Townsville Hospital; Townsville Cancer Centre
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital; Hepatology
    • Woodville, South Australia, Australia, 5011
      • Queen Elizabeth Hospital
  • Tasmania
    • Launceston, Tasmania, Australia, 7250
      • Launceston General Hospital; Gastroenterology Research
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Box Hill Hospital
    • Frankston, Victoria, Australia, 3199
      • Peninsula Oncology Centre; Frankston Private
    • Melbourne, Victoria, Australia, 3000
      • Peter Maccallum Cancer Centre
    • Melbourne, Victoria, Australia, 3004
      • Alfred Hospital
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital
• Austria
  • Innsbruck, Austria, 6020
    • Medizinische Universität Innsbruck
  • Wels, Austria, 4600
    • Klinikum Wels-Grieskirchen
  • Wien, Austria, 1090
    • Medizinische Universität Wien
  • Wien, Austria, 1030
    • Krankenanstalt Rudolfstiftung Wien
• Belgium
  • Antwerpen, Belgium, 2020
    • ZNA Middelheim
  • Brussels, Belgium, 1000
    • Institut Jules Bordet
  • Edegem, Belgium, 2650
    • UZ Antwerpen
  • Gent, Belgium, 9000
    • UZ Gent
  • Hasselt, Belgium, 3500
    • Jessa Zkh (Campus Virga Jesse)
  • Kortrijk, Belgium, 8500
    • AZ Groeninge, Apotheek
• Brazil
  • MG
    • Belo Horizonte, MG, Brazil, 30150-281
      • Trymed Clinical Research
  • RO
    • Ijuí, RO, Brazil, 98700-000
      • Hospital de Caridade de Ijui
  • RS
    • Passo Fundo, RS, Brazil, 99010-260
      • CITO - Centro Integrado de Terapia Onco-Hematológica - Hospital da Cidade de Passo Fundo
    • Porto Alegre, RS, Brazil, 90430-090
      • Clinica de Oncologia de Porto Alegre - CliniOnco
    • Porto Alegre, RS, Brazil, 90035-003
      • Hospital das Clinicas - UFRGS
  • SP
    • Sao Paulo, SP, Brazil, 01308-050
      • Hospital Sirio-Libanes
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BC Cancer Agency Vancouver Centre - PARENT; BC Cancer Agency
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H 2A6
      • Saint Boniface General Hospital; Section of Nephrology BG 007
  • New Brunswick
    • Saint John, New Brunswick, Canada, E2L 4L2
      • Saint John Regional Hospital; Department of Oncology
  • Ontario
    • London, Ontario, Canada, N6A 4G5
      • LHSC - Victoria Hospital; Department of Pediatrics
    • Ottawa, Ontario, Canada, K1H 1C4
      • The Ottawa Hospital Cancer Center; General Campus
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital; Department of Med Oncology
    • Toronto, Ontario, Canada, M4N3M50
      • Toronto Sunnybrook Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3A 1A1
      • Mcgill University - Royal Victoria Hospital; Oncology
    • Montreal, Quebec, Canada, H2L 4M1
      • CHUM Hopital Notre-Dame
    • Ste-Foy, Quebec, Canada, G1V 4G2
      • CHUQ - Hôtel-Dieu de Québec
• Croatia
  • Pula, Croatia, 52100
    • General Hospital Pula
  • Varazdin, Croatia, 42000
    • General Hospital Varazdin
  • Zagreb, Croatia, 10000
    • Clinical Hospital Centre Zagreb
  • Zagreb, Croatia, 10000
    • Clinical Hospital Center Sestre Milosrdnice
• Czechia
  • Brno, Czechia, 656 53
    • Masarykuv onkologicky ustav
  • Hradec Kralove, Czechia, 500 05
    • Fakultni nemocnice Hradec Kralove
  • Olomouc, Czechia, 775 20
    • Fakultni nemocnice Olomouc
  • Ostrava - Poruba, Czechia, 708 52
    • Fakultni nemocnice Ostrava
  • Prague, Czechia, 180 01
    • Nemocnice Na Bulovce
  • Praha, Czechia, 100 34
    • Fakultni nemocnice Kralovske Vinohrady
  • Praha 2, Czechia, 128 08
    • Vseobecna Fakultni Nemocnice V Praze
• Estonia
  • Tallinn, Estonia, 11312
    • East Tallinn Central Hospital; Clinic of Internal Medicine
  • Tallinn, Estonia, 13419
    • North Estonia Medical Centre Foundation
  • Tartu, Estonia, 50406
    • Tartu University Hospital; Clinic of Hematology and Oncology
• France
  • Besançon Cedex, France, 25030
    • CHU Besançon - Hôpital Jean Minjoz
  • Bordeaux, France, 33075
    • Groupe Hospitalier Saint André - Hôpital Saint André
  • Boulogne Billancourt, France, 92104
    • Hôpital Ambroise Paré - Boulogne-Billancourt; Respiratory
  • Lille, France, 59037
    • Hopital Claude Huriez - CHU Lille
  • Marseille, France, 13005
    • Hopital de La Timone
  • Nantes, France, 44093
    • CHU NANTES - Hôtel Dieu; Pharmacy
  • Nice, France, 06202
    • CHU Nice - Hôpital de l'Archet 2
  • Paris, France, 75475
    • Hôpital Saint-Louis
  • Pierre Benite, France, 69495
    • Centre Hospitalier Lyon Sud
  • Rouen, France, 76031
    • CHU de Rouen Hopital; Service de Neurologie
  • Toulouse, France, 31059
    • CHU de Toulouse - Hopital Larrey
• Germany
  • Bochum, Germany, 44791
    • St. Josef-Hospital Universitaetsklinikum
  • Buxtehude, Germany, 21614
    • Elbekliniken Buxtehude GmbH
  • Essen, Germany, 45147
    • Universitätsklinikum Essen
  • Frankfurt, Germany, 60528
    • Universitaetsklinikum Frankfurt
  • Heidelberg, Germany, 69120
    • Universitätsklinikum Heidelberg
  • Kiel, Germany, 24105
    • Universitaetsklinikum Schleswig-Holstein - Campus Kiel; Klinik fuer Allgemeine Innere Medizin
  • Koeln, Germany, 50937
    • Universitätsklinikum Koeln
  • Mainz, Germany, 55131
    • Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz; Apotheke
  • Mannheim, Germany, 68167
    • Klinikum Mannheim GmbH Universitätsklinikum
  • Muenster, Germany, 48157
    • Fachklinik Hornheide
  • Tuebingen, Germany, 72076
    • Universitätsklinikum Tübingen
  • Würzburg, Germany, 97080
    • Universitätsklinikum Würzburg
• Ireland
  • Cork, Ireland
    • Cork University Hospital
  • Dublin, Ireland, 7
    • Mater Private Hospital
  • Dublin, Ireland, 7
    • The Mater Misericordiae Hospital
  • Galway, Ireland
    • University College Hospital
• Israel
  • Beer Sheva, Israel, 8410101
    • Soroka Medical Center
  • Haifa, Israel, 3109600
    • Rambam Health Care Campus
  • Jerusalem, Israel, 9112001
    • Hadassah University Hospital - Ein Kerem
  • Petach Tikva, Israel, 4941492
    • Rabin Medical Center-Beilinson Campus
  • Ramat Gan, Israel, 5265601
    • Chaim Sheba Medical Center
  • Tel Aviv, Israel, 6423906
    • Tel-Aviv Sourasky Medical Center
• Italy
  • Campania
    • Napoli, Campania, Italy, 80131
      • Istituto Nazionale Tumori Fondazione G. Pascale
  • Lazio
    • Roma, Lazio, Italy, 00144
      • Istituto Nazionale Tumori Regina Elena Irccs
    • Roma, Lazio, Italy, 00167
      • IDI-Istituto Dermopatico dell'Immacolata IRCCS
    • Roma, Lazio, Italy, 00133
      • Azienda Ospedaliera Universitaria Policlinico Tor Vergata
  • 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, 20141
      • Istituto Europeo Di Oncologia
    • Milano, Lombardia, Italy, 20132
      • Ospedale San Raffaele
    • Rozzano, Lombardia, Italy, 20089
      • IRCCS Istituto Clinico Humanitas; Farmacia
  • 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
• Mexico
  • Cuernavaca, Mexico, 62290
    • Centro Oncologico Belenus
  • Guadalajara, Mexico, 44280
    • Hospital Civil de Guadalajara Fray Antonio Alcalde
  • Monterrey, Mexico, 64710
    • Centro Regiomontano de Investigación Clínica
  • Morelia, Mexico, 58260
    • Sanatorio la Luz
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Universitair Medisch Centrum Groningen
  • Leiden, Netherlands, 2333 ZA
    • Leids Universitair Medisch Centrum; Cardiology
• New Zealand
  • Christchurch, New Zealand, 8011
    • Christchurch Hospital NZ
  • Wellington, New Zealand, 6012
    • Wellington Hospital
• Norway
  • Stavanger, Norway, 4011
    • Stavanger Universitetssykehus, Helse Stavanger HF
• Poland
  • Olsztyn, Poland, 10-228
    • SPZOZ MSW zWarminsko-MazurskimCen.Onko.wOlsztynie
  • Poznan, Poland, 60-693
    • Przychodnia Med-Polonia Sp. z o.o.
  • Warszawa, Poland, 02-781
    • Centrum Onkologii- Instytut; im. M.Skłodowskiej-Curie
  • Wroclaw, Poland, 53-439
    • Dolnoslaskie Centrum Onkologii
• Portugal
  • Coimbra, Portugal, 3000-075
    • IPO de Coimbra; Servico de Oncologia Medica
  • Evora, Portugal, 7000-811
    • Hospital do Espirito Santo; Servico de Oncologia Medica
  • Lisboa, Portugal, 1649-035
    • Hospital de Santa Maria; Servico de Oncologia Medica
  • Porto, Portugal, 4200-072
    • IPO do Porto; Servico de Oncologia Medica
• Russian Federation
  • Krasnodar, Russian Federation, 350040
    • Krasnodar City Oncology Center
  • Moscow, Russian Federation, 115478
    • FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"
  • St. Petersburg, Russian Federation, 197758
    • Scientific Research Oncology Institute named after N.N. Petrov
  • Moskovskaja Oblast
    • Moscovskaya Oblast, Moskovskaja Oblast, Russian Federation, 143423
      • Moscow City Oncology Hospital #62
• Serbia
  • Belgrade, Serbia, 11000
    • Institute of Oncology and Radiology of Serbia
  • Belgrade, Serbia, 11040
    • Military Medical Academy
  • Belgrade, Serbia, 11070
    • Clinical Center Bezanijska Kosa
  • Sremska Kamenica, Serbia, 21204
    • Institute for oncology of Vojvodina
• South Africa
  • Cape Town, South Africa, 7700
    • GVI Rondebosch Oncology Centre
  • Groenkloof, South Africa, 0181
    • Mary Potter Oncology Centre
  • Observatory, South Africa, 7925
    • Groote Schuur Hospital Radiation Oncology Department; Department of Radiation Oncology
  • Pretoria, South Africa, 0001
    • University of Pretoria Oncology Department
  • Sandton, South Africa, 2196
    • Sandton Oncology Medical Group
• Spain
  • Barcelona, Spain, 08908
    • Institut Catala d Oncologia Hospital Duran i Reynals
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu; i Sant Pau
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon
  • Valencia, Spain, 46026
    • Hospital Universitari I Politecnic La Fe
  • LA Coruña
    • Santiago de Compostela, LA Coruña, Spain, 15706
      • Hospital Clinico Universitario de Santiago
  • Malaga
    • Marbella, Malaga, Spain, 29600
      • Hospital Costa del Sol; Servicio de Oncologia
• Sweden
  • Jönköping, Sweden, 551 85
    • Lanssjukhuset Ryhov
  • Umea, Sweden, 901 850
    • Norrlands Universitetssjukhus
  • Växjö, Sweden, 351 85
    • Centrallasarettet Vaxjo
• Switzerland
  • Lausanne, Switzerland, 1011
    • CHUV; Departement d'Oncologie
• Ukraine
  • Dnipropetrovsk, Ukraine, 49102
    • CI Dnipropetrovsk CMCH 4 of Dnipropetrovsk RC Dept of Chemotherapy SI Dnipropetrovsk MA of MOHU
  • Lviv, Ukraine, 79031
    • Lviv State Oncological Regional Treatment and Diagnostic Center
• United Kingdom
  • 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
  • Kings Lynn, United Kingdom, PE30 4ET
    • Queen Elizabeth Hospital
  • London, United Kingdom, SE1 9RT
    • Guys and St Thomas NHS Foundation Trust, Guys Hospital
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham University Hospitals City Campus
  • Oxford, United Kingdom, OX3 7LJ
    • Churchill Hospital
  • Truro, United Kingdom, TR1 3LQ
    • Royal Cornwall Hospital
  • Wolverhampton, United Kingdom, WV10 0QP
    • New Cross Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • California
    • California City, California, United States, 90095
      • UCLA Department of Medicine; Division of Hematology / Oncology
    • Hayward, California, United States, 94545
      • Kaiser Permanente - Hayward
    • Irvine, California, United States, 92604
      • UCLA Hematology Oncology - Irvine
    • La Jolla, California, United States, 92093
      • UCSD Moores Cancer Center
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic and Research Institute - W LA Office
    • Los Angeles, California, United States, 90095
      • Cancer Center Of Santa Barbara; Network Clinical Research Specialist
    • Los Angeles, California, United States, 90095
      • TRIO-US Network Administration; Network Clinical Research Specialist
    • Oakland, California, United States, 94611
      • Kaiser Permanente - Oakland
    • Oakland, California, United States, 94611
      • Kaiser Foundation Hospital - Oakland (W. MacArthur)
    • Pasadena, California, United States, 91105
      • UCLA Healthcare/Pasadena Oncology
    • Roseville, California, United States, 95661
      • Kaiser Permanente - Roseville
    • Sacramento, California, United States, 95814
      • Kaiser Permanente Sacramento Medical Center
    • San Francisco, California, United States, 94115
      • Kaiser Permanente
    • San Jose, California, United States, 95119
      • K. Permanente - San Jose
    • San Luis Obispo, California, United States, 93401
      • Coastal Integrative Cancer Care
    • Santa Clara, California, United States, 95051
      • Kaiser Permanente - Santa Clara
    • South San Francisco, California, United States, 94080
      • Kaiser Permanente - South San Francisco
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine; Stanford Hospital Pharmacy
    • Valencia, California, United States, 91355
      • UCLA Cancer Center Hema/Oncol
    • Vallejo, California, United States, 94589
      • Kaiser Permanente - Vallejo
    • Walnut Creek, California, United States, 94596
      • Kaiser Permanente - Walnut Creek
    • Westlake Village, California, United States, 91361
      • UCLA Hematology Oncology - Westlake
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
    • Grand Junction, Colorado, United States, 81501
      • St. Mary's Hospital Regional Cancer Center
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists - Broadway
    • Hollywood, Florida, United States, 33021
      • Memorial Healthcare System
    • Sarasota, Florida, United States, 34232
      • GulfCoast Oncology
  • Illinois
    • Park Ridge, Illinois, United States, 60068
      • Oncology Specialists, S.C.
  • Indiana
    • Goshen, Indiana, United States, 46526
      • Indiana University Health; Goshen Center for Cancer Care
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Department of Medicine; Division of Infectious Diseases
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • U of L - Physicians Pulmonology; Dept of Neuroradiology and Dept of Diagnostic Radiology
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Institute
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • St. Luke's Hospital
    • Kansas City, Missouri, United States, 64131
      • University of Kansas Medical Center; Cancer Center
    • Saint Louis, Missouri, United States, 63110
      • Washington University; Dept of Medicine/Div of Medical Oncology
  • New Jersey
    • Randolph, New Jersey, United States, 07869
      • Atlantic Health Systems; Pediatrics
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10016
      • New York University Medical Center PRIME; NYU Clinical Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center; Oncology
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Health System
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • MUSC Hollings Cancer Center/cannon Park Place; Attn: Tamara Saunders
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • West Clinic
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology PLLC - Nashville (20th Ave)
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Mary Babb Randolph Cancer Center

Participation Criteria

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:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 Vemurafenib; Participants with completely resected Stage IIC, IIIA, or IIIB cutaneous melanoma) received vemurafenib, 960 milligrams (mg) twice daily, in 28-day cycles, for up to 52 weeks	Drug: Vemurafenib; 4 tablets of vemurafenib 240 mg each (total 960 mg) were administered orally as per the schedule specified in the respective arm.; Other Names: RO5185426/F17, Zelboraf
Placebo Comparator: Cohort 1 Placebo; Participants with completely resected Stage IIC, IIIA, or IIIB cutaneous melanoma) received vemurafenib-matching placebo twice daily, in 28-day cycles, for up to 52 weeks	Drug: Placebo; Placebo matching to vemurafenib were administered orally as per the schedule specified in the respective arm.
Experimental: Cohort 2 Vemurafenib; Participants with Stage IIIC cutaneous melanoma received vemurafenib, 960 mg twice daily, in 28-day cycles, for up to 52 weeks	Drug: Vemurafenib; 4 tablets of vemurafenib 240 mg each (total 960 mg) were administered orally as per the schedule specified in the respective arm.; Other Names: RO5185426/F17, Zelboraf
Placebo Comparator: Cohort 2 Placebo; Participants with Stage IIIC cutaneous melanoma received vemurafenib-matching placebo twice daily, in 28-day cycles, for up to 52 weeks	Drug: Placebo; Placebo matching to vemurafenib were administered orally as per the schedule specified in the respective arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
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)
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)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Ascierto PA, Lewis KD, Di Giacomo AM, Demidov L, Mandala M, Bondarenko I, Herbert C, Mackiewicz A, Rutkowski P, Guminski A, Simmons B, Ye C, Hooper G, Wongchenko MJ, Goodman GR, Yan Y, Schadendorf D. Prognostic impact of baseline tumour immune infiltrate on disease-free survival in patients with completely resected, BRAFv600 mutation-positive melanoma receiving adjuvant vemurafenib. Ann Oncol. 2020 Jan;31(1):153-159. doi: 10.1016/j.annonc.2019.10.002.
• Maio M, Lewis K, Demidov L, Mandala M, Bondarenko I, Ascierto PA, Herbert C, Mackiewicz A, Rutkowski P, Guminski A, Goodman GR, Simmons B, Ye C, Yan Y, Schadendorf D; BRIM8 Investigators. Adjuvant vemurafenib in resected, BRAFV600 mutation-positive melanoma (BRIM8): a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. Lancet Oncol. 2018 Apr;19(4):510-520. doi: 10.1016/S1470-2045(18)30106-2. Epub 2018 Feb 21. Erratum In: Lancet Oncol. 2018 Apr;19(4):e184.

Study record dates

Study Major Dates

• Study Start (Actual): September 24, 2012
• Primary Completion (Actual): June 23, 2017
• Study Completion (Actual): July 13, 2018

Study Registration Dates

• First Submitted: August 15, 2012
• First Submitted That Met QC Criteria: August 15, 2012
• First Posted (Estimate): August 17, 2012

Study Record Updates

• Last Update Posted (Actual): July 23, 2019
• Last Update Submitted That Met QC Criteria: July 11, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Vemurafenib
• Other Study ID Numbers: GO27826; 2011-004011-24 (EudraCT Number)