Adjuvant Encorafenib and Binimetinib in High-risk Stage II Melanoma With a BRAF Mutation.
COLUMBUS-AD
Adjuvant Encorafenib & Binimetinib vs. Placebo in Fully Resected Stage IIB/C BRAF V600E/K Mutated Melanoma: a Randomized Triple-blind Phase III Study in Collaboration With the EORTC Melanoma Group
1 other identifier
interventional
815
21 countries
149
Brief Summary
The purpose of the Columbus-AD study is to evaluate the efficacy and safety of 12 months of encorafenib in combination with binimetinib in adjuvant setting of BRAF V600E/K mutant stage IIB/C melanoma versus the current standard of care (surveillance).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started May 2022
Longer than P75 for phase_3
149 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 14, 2022
CompletedFirst Posted
Study publicly available on registry
March 8, 2022
CompletedStudy Start
First participant enrolled
May 2, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
May 2, 2035
November 22, 2023
November 1, 2023
4.9 years
February 14, 2022
November 21, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Recurrence-free survival (RFS)
RFS is defined as the time between the date of randomization and the date of 1) first recurrence (local, regional, or a distant metastasis), 2) new melanoma that is known to be either ulcerated, thick (Breslow thickness\>1 mm) or requiring a treatment other than surgery or 3) death (whatever the cause), whichever occurs first.
Approximately 4.4 years from the accrual of the first patient.
Secondary Outcomes (21)
Distant metastasis-free survival (DMFS)
Approximately 6.0 years from first patient in
Overall survival (OS)
Approximately 10 years from first Patient In.
Safety - Incidence, nature, severity and seriousness of treatment emergent adverse events (TEAEs)
From the signing of the ICF up to 30 days after end of treatment- approximately 14.5 months
Safety -Incidence, nature and severity of cutaneous malignancies by dermatological examination
From the signing of ICF to study completion- approximately 10 years from last patient in
Safety -Incidence of Serious adverse events (SAEs)
From the signing of the ICF to study completion- approximately 10 years from last patient in
- +16 more secondary outcomes
Study Arms (2)
Arm A
EXPERIMENTALEncorafenib and Binimetinib
Arm B
PLACEBO COMPARATORPlacebo to match Encorafenib Placebo to match Binimetinib
Interventions
Encorafenib 450 mg (6 × 75 mg capsules) once daily (QD) and binimetinib 45 mg (3 x 15 mg tablets) twice daily (BID) orally for a maximum of 12 months.
Encorafenib (6 × 75 mg placebo capsules) QD and binimetinib (3 × 15 mg placebo tablets) BID placebos orally for a maximum of 12 months.
Eligibility Criteria
You may qualify if:
- Pre-Screening
- Male or female ≥ 18 years of age;
- Surgically resected, with tumour free margins, and histologically/pathologically confirmed new diagnosis of stage II (pT3b-pT4bN0) cutaneous melanomaa;
- Sentinel node (SN) biopsy within 14 weeks from initial diagnosis of melanoma.
- Sentinel node (SN) staged node negative (pN0);
- Available tumour sample for central determination of the BRAF V600E/K mutation.
- Screening
- Melanoma confirmed centrally to be BRAF V600E/K mutation-positive;
- Participant still free of disease as evidenced by the required baseline imaging and physical/dermatological assessments performed respectively within 6 weeks and 2 weeks before randomization (Day 1);
- No more than 12 weeks elapsed between full surgical resection (including SLNB) and randomization;
- Recovered from definitive surgery (e.g., complete wound healing, no uncontrolled wound infections or indwelling drains);
- ECOG performance status of 0 or 1;
- Adequate haematological function as defined as Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L and Hemoglobin
- ≥ 9.0 g/dL;
- Adequate renal function as defined as Serum creatinine ≤ 1.5 × ULN; or calculated creatinine clearance ≥ 50 mL/min;
- +6 more criteria
You may not qualify if:
- Pre-screening
- Unknown ulceration status;
- Uveal and mucosal melanoma;
- Clinically apparent metastases (N+/M1);
- Microsatellites, satellites and/or in-transit metastases,
- Local (scar) recurrences.
- Screening
- Breast feeding women;
- Pregnant women;
- History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO;
- History of thromboembolic or cerebrovascular events ≤ 12 weeks prior to randomization;
- History of previous or concurrent malignancy within preceding 3 years or any condition with a life expectancy of less than 5 years;
- Participants with a prior cancer associated with RAS mutation;
- Prior systemic anticancer therapy for melanoma or radiotherapy for melanoma;
- Hypersensitivity to the study drugs or to any of the excipients;
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (155)
Centro Oncologico Korben
CABA, Buenos Aires, C1426, Argentina
Centro de Investigaciones Medicas Mar del Plata
Mar del Plata, Buenos Aires, B7600FYK, Argentina
Fundacion CIDEA
Ciudad Autonoma Bs As, Ciudad Autonoma Buenos Aires, C1121ABE, Argentina
Sanatorio Britanico S.A.
Rosario, Santa Fe Province, 2000, Argentina
Instituto de Oncologia de Rosario
Rosario, Santa Fe Province, S2000KZE, Argentina
Hospital Aleman
Ciudad Autonoma Buenos Aires, C1118AAT, Argentina
Instituto Medico Especializado Alexander Fleming
Ciudad Autonoma Buenos Aires, C1426ANZ, Argentina
Clinica Adventista Belgrano
Ciudad Autonoma Buenos Aires, C1430EGF, Argentina
Westmead Hospital
Sydney, New South Wales, 2145, Australia
Melanoma Institute Australia
Wollstonecraft, New South Wales, 2065, Australia
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102, Australia
Adelaide Oncology & Haematolog, Calvary North Adelaide Hospital
North Adelaide, South Australia, 5006, Australia
Box Hill Hospital
Box Hill, Victoria, 3128, Australia
Austin Health
Heidelberg, Victoria, 3084, Australia
The Alfred Hospital
Prahran, Victoria, 3181, Australia
Hollywood Private Hospital
Nedlands, Western Australia, 6009, Australia
Sir Charles Gairdner Hospital
Nedlands, Western Australia, 6009, Australia
Landeskrankenhaus - Universitaetsklinikum Graz
Graz, 8036, Austria
Krankenhaus der Elisabethinen Linz
Linz, 4020, Austria
Universitätsklinikum St.Pölten-Lilienfeld
Sankt Pölten, 3100, Austria
AKH - Medizinische Universität Wien
Vienna, 1090, Austria
Institut Jules Bordet
Anderlecht, 1070, Belgium
ZNA Middelheim
Antwerp, 2020, Belgium
Universitair Ziekenhuis Brussel
Brussels, 1090, Belgium
Cliniques Universitaires Saint-Luc
Brussels, 1200, Belgium
UZ Gent
Ghent, 9000, Belgium
ZNA
Merksem, 2170, Belgium
Vitaz
Sint-Niklaas, 9100, Belgium
CHU UCL Namur
Yvoir, 5530, Belgium
AMO - Assistência Multidisciplinar em Oncologia
Salvador, Estado de Bahia, 41950-640, Brazil
Hospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer
Curitiba, Paraná, 81520-060, Brazil
Instituto de Cancer de Londrina
Londrina, Paraná, 86015-520, Brazil
Hospital de Clínicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90035-903, Brazil
HGB - Hospital Giovanni Battista - Mãe de Deus Center
Porto Alegre, Rio Grande do Sul, 90110-270, Brazil
Instituto de Oncologia Saint Gallen
Santa Cruz do Sul, Rio Grande do Sul, 96810-110, Brazil
CEPON - Centro de Pesquisas Oncológicas de Santa Catarina
Florianópolis, Santa Catarina, 88034-000, Brazil
Fundação Doutor Amaral Carvalho
Jaú, São Paulo, 17210-120, Brazil
CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia
Santo André, São Paulo, 09060-870, Brazil
A. C. Camargo Cancer Center
São Paulo, São Paulo, 01509-900, Brazil
London Health Sciences Centre (LHSC) - Victoria Hospital
London, Ontario, N6A 5W9, Canada
Toronto Sunnybrook Hospital
Toronto, Ontario, M4N 3M5, Canada
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9, Canada
CIUSSS du Centre Ouest de l'lle de Montreal
Montreal, Quebec, H3T 1E2, Canada
Fakultni nemocnice Hradec Kralove
Hradec Králové, 500 05, Czechia
Fakultni nemocnice Olomouc
Olomouc, 79900, Czechia
Fakultni nemocnice Ostrava
Ostrava - Poruba, 708 52, Czechia
Fakultni nemocnice Kralovske Vinohrady
Prague, 100 34, Czechia
Vseobecna fakultni nemocnice v Praze
Prague, 128 08, Czechia
CHU Nice - Hopital de l Archet 2
Nice, Alpes Maritimes, 06202, France
Hôpital de la Timone
Marseille, Bouches-du-Rhône, 13385, France
CHU de Dijon - Hôpital du Bocage
Dijon, Cote dÝOr, 21079, France
CHU de Bordeaux - Hôpital Saint André
Bordeaux, Gironde, 33075, France
Institut Claudius Regaud - Oncopole
Toulouse, Haute Garonne, 31059, France
Hôpital Ambroise Paré
Boulogne-Billancourt, Hauts De Seine, 92100, France
CRLCC Eugene Marquis
Rennes, Ille Et Vilaine, 35042, France
CHU Tours - Hôpital Trousseau
Chambray-lès-Tours, Indre Et Loire, 37170, France
CHU de Grenoble - Hôpital André Michallon
La Tronche, Isere, 38700, France
CHU Nantes - Hôtel Dieu
Nantes, Loire Atlantique, 44093, France
Hopital Claude Huriez - CHU Lille
Lille, Nord, 59037, France
Hôpital Saint-Louis
Paris, Paris, 75010, France
CHU Saint Etienne - Hôpital Nord
Saint-Étienne-de-Montluc, Pays de la Loire Region, 42055, France
CAC Clermont-Ferrand Centre Jean Perrin
Clermont-Ferrand, Puy De Dome, 63000, France
Centre Hospitalier de Pau - Hôpital François Mitterrand
Pau, Pyrenees Atlantiques, 64046, France
Centre Hospitalier Lyon Sud
Pierre-Bénite, Rhone, 69495, France
CHU de Rouen - Hôpital Charles Nicolle
Rouen, Seine Maritime, 76031, France
Institut Gustave Roussy
Villejuif, Val De Marne, 94805, France
CHU Poitiers - Hôpital la Milétrie
Poitiers, Vienne, 86021, France
Universitaetsklinikum Heidelberg
Heidelberg, Baden-Wurttemberg, 69120, Germany
Universitaetsklinikum Wuerzburg
Würzburg, Bavaria, 97080, Germany
Elbekliniken Buxtehude GmbH
Buxtehude, Lower Saxony, 21614, Germany
Universitaetsklinikum Carl Gustav Carus TU Dresden
Dresden, Saxony, 01307, Germany
Universitaetsklinikum Schleswig-Holstein
Kiel, Schleswig-Holstein, 24105, Germany
Universitaetsklinikum Hamburg-Eppendorf
Hamburg, 20246, Germany
General Hospital of Athens Laiko
Athens, 11527, Greece
Metropolitan Hospital
Neo Faliro, 18547, Greece
Bioclinic Thessaloniki
Thessaloniki, 54622, Greece
Anticancer Hospital of Thessaloniki " Theagenio"
Thessaloniki, 54639, Greece
Interbalkan Hospital of Thessaloniki
Thessaloniki, 57001, Greece
Semmelweis Egyetem
Budapest, 1085, Hungary
Orszagos Onkologiai Intezet
Budapest, 1122, Hungary
Debreceni Egyetem
Debrecen, 4032, Hungary
Petz Aladar Egyetemi Oktato Korhaz
Győr, 9023, Hungary
Pecsi Tudomanyegyetem
Pécs, 7632, Hungary
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
Szeged, 6720, Hungary
IRCCS Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori "Dino Amadori" - IRST
Meldola, Forli - Cesena, 47014, Italy
Ospedale San Vincenzo
Taormina, Messina, 98039, Italy
Istituto Nazionale Tumori Fondazione G. Pascale
Naples, Napoli, 80131, Italy
IRCCS Centro di Riferimento Oncologico
Aviano, Pordenone, 33081, Italy
Istituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico Bari
Bari, 70124, Italy
Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)
Bergamo, 24127, Italy
Azienda Sanitaria Ospedaliera S.Croce e Carle
Cuneo, 12100, Italy
IRCCS Ospedale Policlinico San Martino
Genova, 16132, Italy
Ospedale San Raffaele
Milan, 20132, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, 20133, Italy
IEO Istituto Europeo di Oncologia
Milan, 20141, Italy
IOV - Istituto Oncologico Veneto IRCCS
Padua, 35128, Italy
Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone
Palermo, 90127, Italy
Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia
Perugia, 06156, Italy
Azienda Ospedaliero Universitaria Pisana
Pisa, 56126, Italy
Istituto Nazionale Tumori Regina Elena IRCCS
Roma, 00144, Italy
IDI-Istituto Dermopatico dell'Immacolata IRCCS
Roma, 00167, Italy
Policlinico Universitario di Sassari
Sassari, 07100, Italy
A.O.U. Senese Policlinico Santa Maria alle Scotte
Siena, 53100, Italy
Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino
Torino, 10126, Italy
Azienda Sanitaria Universitaria Friuli Centrale
Udine, 33100, Italy
Antoni van Leeuwenhoek
Amsterdam, 1066 CX, Netherlands
Universitair Medisch Centrum Groningen (UMCG)
Groningen, 9713 GZ, Netherlands
Leids Universitair Medisch Centrum
Leiden, 2333 ZA, Netherlands
Maastricht University Medical Center
Maastricht, 6202 AZ, Netherlands
Radboudumc
Nijmegen, 6525 GA, Netherlands
Erasmus MC
Rotterdam, 3015 GD, Netherlands
UMC Utrecht
Utrecht, 3508 GA, Netherlands
Isala
Zwolle, 8025 AB, Netherlands
Ålesund Hospital
Ålesund, 6017, Norway
Oslo University Hospital
Oslo, 0424, Norway
Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie - Panstwowy Instytut Badawczy
Gliwice, 44-102, Poland
Przychodnia Lekarska Komed
Konin, 62-500, Poland
Centrum Onkologii-Instytut im. M. Sklodowskiej-Curie
Krakow, 31-115, Poland
Wielkopolskie Centrum Onkologii
Poznan, 61-866, Poland
Centrum Medyczne Pratia Poznan
Skórzewo, 60-185, Poland
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
Warsaw, 02-781, Poland
Dolnoslaskie Centrum Onkologii
Wroclaw, 53-413, Poland
Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE
Lisbon, 1099-023, Portugal
Centro Hospitalar de Lisboa Norte, E.P.E. - Hospital de Santa Maria
Lisbon, 1649-035, Portugal
Instituto Português de Oncologia do Porto Francisco Gentil, EPE
Porto, 4200-072, Portugal
S.C Medisprof S.R.L
Cluj-Napoca, 400641, Romania
S.C Centrul de Oncologie Sf. Nectarie S.R.L
Craiova, 200542, Romania
Institutul Regional de Oncologie Iasi
Iași, 700483, Romania
Clinical Center "Bezanijska kosa"
Belgrade, 11000, Serbia
Institute of Oncology and Radiology of Serbia
Belgrade, 11000, Serbia
Military Medical Academy
Belgrade, 11000, Serbia
Oncology Institute of Vojvodina
Kamenitz, 21204, Serbia
Clinical Center Kragujevac
Kragujevac, 34000, Serbia
Clinical Center Nis
Niš, 18000, Serbia
National Hospital Oncology
Bloemfontein, Free State, 9301, South Africa
Johese Clinical Research: Midstream
Centurion, Gauteng, 1692, South Africa
Sandton Oncology Medical Group
Johannesburg, Gauteng, 2196, South Africa
ICO Badalona - Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, 08916, Spain
ICO l'Hospitalet - Hospital Duran i Reynals
L'Hospitalet de Llobregat, Barcelona, 08908, Spain
Hospital Universitario Virgen de la Arrixaca
El Palmar, Murcia, 30120, Spain
Hospital Universitari Vall d'Hebron
Barcelona, 08035, Spain
Hospital Clinic de Barcelona
Barcelona, 08036, Spain
Hospital Universitario Reina Sofia
Córdoba, 14004, Spain
Hospital General Universitario Gregorio Marañon
Madrid, 28007, Spain
Hospital Universitario Ramon y Cajal
Madrid, 28034, Spain
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
Centro Integral Oncologico Clara Campal
Madrid, 28050, Spain
Hospital Regional Universitario de Malaga
Málaga, 29010, Spain
Hospital Clinico Universitario de Valencia
Valencia, 46010, Spain
Hospital General Universitario de Valencia
Valencia, 46014, Spain
Karolinska University Hospital
Stockholm, 17176, Sweden
Norrlands Universitetssjukhus
Umeå, 901 87, Sweden
Universitaetsspital Zuerich
Zurich, 8091, Switzerland
Royal Preston Hospital
Preston, Lancashire, PR2 9HT, United Kingdom
Northern Centre for Cancer Care
Newcastle upon Tyne, Tyne & Wear, NE7 7DN, United Kingdom
Related Publications (1)
van Akkooi AC, Hauschild A, Long GV, Mandala M, Kicinski M, Govaerts AS, Klauck I, Ouali M, Lorigan PC, Eggermont AM. COLUMBUS-AD: phase III study of adjuvant encorafenib + binimetinib in resected stage IIB/IIC BRAF V600-mutated melanoma. Future Oncol. 2023 Sep;19(30):2017-2027. doi: 10.2217/fon-2023-0414. Epub 2023 Sep 4.
PMID: 37665297DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Alexander C.J. van AKKOOI, MD, PhD
European Organisation for Research and Treatment of Cancer - EORTC
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 14, 2022
First Posted
March 8, 2022
Study Start
May 2, 2022
Primary Completion (Estimated)
March 31, 2027
Study Completion (Estimated)
May 2, 2035
Last Updated
November 22, 2023
Record last verified: 2023-11
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, ICF
- Time Frame
- * Study protocol/Informed Consent Form will be made available in Clinical Trial.gov 30 days after the time of CHMP opinion or up to a maximum of 1 year after the end of the trial whichever is earlier. * CSR and SAP: 30 days after the time of CHMP opinion or up to a maximum of 1 year after the end of the trial whichever is earlier.
- Access Criteria
- Pierre Fabre corporate portal
Access to de-identified patient-level data in response to scientifically valid research proposals will be provided 30 days after CHMP opinion. All requests from qualified researchers for access to Columbus AD clinical data and information will be managed through a dedicated Pierre Fabre portal.