Adjuvant Encorafenib and Binimetinib in High-risk Stage II Melanoma With a BRAF Mutation.
NCT ID: NCT05270044
Last Updated: 2023-11-22
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE3
815 participants
INTERVENTIONAL
2022-05-02
2035-05-02
Brief Summary
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Detailed Description
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Participants with completely resected cutaneous melanoma and documented BRAF V600E/K status by central assay will be randomized 1 to 1 to receive either treatment with encorafenib and binimetinib or their two placebos for 12 months. Patients will be stratified according to the stage of the disease according to AJCC version 8 between:
* stage IIB (i.e., pT3b or pT4a)
* stage IIC (i.e., pT4b).
The long-term evaluation of all endpoints (including information about the occurrence of new treatment-related adverse events, if any) will take place 10 years from the randomization of the last patient.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
TRIPLE
Study Groups
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Arm A
Encorafenib and Binimetinib
Encorafenib and Binimetinib
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.
Arm B
Placebo to match Encorafenib Placebo to match Binimetinib
Placebo to match Encorafenib ; Placebo to match Binimetinib
Encorafenib (6 × 75 mg placebo capsules) QD and binimetinib (3 × 15 mg placebo tablets) BID placebos orally for a maximum of 12 months.
Interventions
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Encorafenib and Binimetinib
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.
Placebo to match Encorafenib ; Placebo to match Binimetinib
Encorafenib (6 × 75 mg placebo capsules) QD and binimetinib (3 × 15 mg placebo tablets) BID placebos orally for a maximum of 12 months.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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;
* Adequate electrolytes, defined as serum potassium and magnesium levels within institutional normal limits;
* Adequate hepatic function as defined as Serum total bilirubin ≤ 1.5 x ULN and \< 2 mg/dL, Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ 2.5 x ULN;
* Adequate cardiac function as defined as LVEF ≥ 50% as determined by MUGA scan or echocardiogram and Mean triplicate QTcF value ≤ 480 msec and no history of QT syndrome;
* Adequate coagulation function, defined as INR ≤1.5× ULN unless the patient is receiving anticoagulant therapy as long as PT or aPTT is within the therapeutic range;
* Negative serum β-HCG test (female patient of childbearing potential only) performed within 3 days prior to Day 1;
* Female patients of child-bearing potential and male patients must agree to follow the protocol's contraception guidance during the treatment period and for ≥30 days after last administration.
Exclusion Criteria
* 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;
* Participants with severe lactose intolerance (e.g., Rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption);
* Impaired cardiovascular function or clinically significant cardiovascular diseases;
* Neuromuscular disorders that are associated with CK \> ULN (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy);
* Non-infectious pneumonitis and Interstitial Lung Disease;
* Positive SARs-CoV-2 or variants of SARs-CoV2 RT-PCR test at screening or suspected to be infected with SARs-CoV2 or variants of SARsCoV2 with confirmation pending;
* Active bacterial, fungal, or viral infection, including, but not limited to HBV, HCV, and known HIV or AIDS-related illness, or an infection requiring systemic therapeutic treatment within 2 weeks prior to randomization.
18 Years
ALL
No
Sponsors
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European Organisation for Research and Treatment of Cancer - EORTC
NETWORK
Pierre Fabre Medicament
INDUSTRY
Responsible Party
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Principal Investigators
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Alexander C.J. van AKKOOI, MD, PhD
Role: STUDY_CHAIR
European Organisation for Research and Treatment of Cancer - EORTC
Locations
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Centro Oncologico Korben
CABA, Buenos Aires, Argentina
Centro de Investigaciones Medicas Mar del Plata
Mar del Plata, Buenos Aires, Argentina
Fundacion CIDEA
Ciudad Autonoma Bs As, Ciudad Autonoma Buenos Aires, Argentina
Sanatorio Britanico S.A.
Rosario, Santa Fe Province, Argentina
Instituto de Oncologia de Rosario
Rosario, Santa Fe Province, Argentina
Hospital Aleman
Ciudad Autonoma Buenos Aires, , Argentina
Instituto Medico Especializado Alexander Fleming
Ciudad Autonoma Buenos Aires, , Argentina
Clinica Adventista Belgrano
Ciudad Autonoma Buenos Aires, , Argentina
Westmead Hospital
Sydney, New South Wales, Australia
Melanoma Institute Australia
Wollstonecraft, New South Wales, Australia
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia
Adelaide Oncology & Haematolog, Calvary North Adelaide Hospital
North Adelaide, South Australia, Australia
Box Hill Hospital
Box Hill, Victoria, Australia
Austin Health
Heidelberg, Victoria, Australia
The Alfred Hospital
Prahran, Victoria, Australia
Hollywood Private Hospital
Nedlands, Western Australia, Australia
Sir Charles Gairdner Hospital
Nedlands, Western Australia, Australia
Landeskrankenhaus - Universitaetsklinikum Graz
Graz, , Austria
Krankenhaus der Elisabethinen Linz
Linz, , Austria
Universitätsklinikum St.Pölten-Lilienfeld
Sankt Pölten, , Austria
AKH - Medizinische Universität Wien
Vienna, , Austria
Institut Jules Bordet
Anderlecht, , Belgium
ZNA Middelheim
Antwerp, , Belgium
Universitair Ziekenhuis Brussel
Brussels, , Belgium
Cliniques Universitaires Saint-Luc
Brussels, , Belgium
UZ Gent
Ghent, , Belgium
ZNA
Merksem, , Belgium
Vitaz
Sint-Niklaas, , Belgium
CHU UCL Namur
Yvoir, , Belgium
AMO - Assistência Multidisciplinar em Oncologia
Salvador, Estado de Bahia, Brazil
Hospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer
Curitiba, Paraná, Brazil
Instituto de Cancer de Londrina
Londrina, Paraná, Brazil
Hospital de Clínicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, Brazil
HGB - Hospital Giovanni Battista - Mãe de Deus Center
Porto Alegre, Rio Grande do Sul, Brazil
Instituto de Oncologia Saint Gallen
Santa Cruz do Sul, Rio Grande do Sul, Brazil
CEPON - Centro de Pesquisas Oncológicas de Santa Catarina
Florianópolis, Santa Catarina, Brazil
Fundação Doutor Amaral Carvalho
Jaú, São Paulo, Brazil
CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia
Santo André, São Paulo, Brazil
A. C. Camargo Cancer Center
São Paulo, São Paulo, Brazil
London Health Sciences Centre (LHSC) - Victoria Hospital
London, Ontario, Canada
Toronto Sunnybrook Hospital
Toronto, Ontario, Canada
Princess Margaret Cancer Centre
Toronto, Ontario, Canada
CIUSSS du Centre Ouest de l'lle de Montreal
Montreal, Quebec, Canada
Fakultni nemocnice Hradec Kralove
Hradec Králové, , Czechia
Fakultni nemocnice Olomouc
Olomouc, , Czechia
Fakultni nemocnice Ostrava
Ostrava - Poruba, , Czechia
Fakultni nemocnice Kralovske Vinohrady
Prague, , Czechia
Vseobecna fakultni nemocnice v Praze
Prague, , Czechia
CHU Nice - Hopital de l Archet 2
Nice, Alpes Maritimes, France
Hôpital de la Timone
Marseille, Bouches-du-Rhône, France
CHU de Dijon - Hôpital du Bocage
Dijon, Cote dÝOr, France
CHU de Bordeaux - Hôpital Saint André
Bordeaux, Gironde, France
Institut Claudius Regaud - Oncopole
Toulouse, Haute Garonne, France
Hôpital Ambroise Paré
Boulogne-Billancourt, Hauts De Seine, France
CRLCC Eugene Marquis
Rennes, Ille Et Vilaine, France
CHU Tours - Hôpital Trousseau
Chambray-lès-Tours, Indre Et Loire, France
CHU de Grenoble - Hôpital André Michallon
La Tronche, Isere, France
CHU Nantes - Hôtel Dieu
Nantes, Loire Atlantique, France
Hopital Claude Huriez - CHU Lille
Lille, Nord, France
Hôpital Saint-Louis
Paris, Paris, France
CHU Saint Etienne - Hôpital Nord
Saint-Étienne-de-Montluc, Pays de la Loire Region, France
CAC Clermont-Ferrand Centre Jean Perrin
Clermont-Ferrand, Puy De Dome, France
Centre Hospitalier de Pau - Hôpital François Mitterrand
Pau, Pyrenees Atlantiques, France
Centre Hospitalier Lyon Sud
Pierre-Bénite, Rhone, France
CHU de Rouen - Hôpital Charles Nicolle
Rouen, Seine Maritime, France
Institut Gustave Roussy
Villejuif, Val De Marne, France
CHU Poitiers - Hôpital la Milétrie
Poitiers, Vienne, France
Universitaetsklinikum Heidelberg
Heidelberg, Baden-Wurttemberg, Germany
Universitaetsklinikum Wuerzburg
Würzburg, Bavaria, Germany
Elbekliniken Buxtehude GmbH
Buxtehude, Lower Saxony, Germany
Universitaetsklinikum Carl Gustav Carus TU Dresden
Dresden, Saxony, Germany
Universitaetsklinikum Schleswig-Holstein
Kiel, Schleswig-Holstein, Germany
Universitaetsklinikum Hamburg-Eppendorf
Hamburg, , Germany
General Hospital of Athens Laiko
Athens, , Greece
Metropolitan Hospital
Neo Faliro, , Greece
Bioclinic Thessaloniki
Thessaloniki, , Greece
Anticancer Hospital of Thessaloniki " Theagenio"
Thessaloniki, , Greece
Interbalkan Hospital of Thessaloniki
Thessaloniki, , Greece
Semmelweis Egyetem
Budapest, , Hungary
Orszagos Onkologiai Intezet
Budapest, , Hungary
Debreceni Egyetem
Debrecen, , Hungary
Petz Aladar Egyetemi Oktato Korhaz
Győr, , Hungary
Pecsi Tudomanyegyetem
Pécs, , Hungary
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
Szeged, , Hungary
IRCCS Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori "Dino Amadori" - IRST
Meldola, Forli - Cesena, Italy
Ospedale San Vincenzo
Taormina, Messina, Italy
Istituto Nazionale Tumori Fondazione G. Pascale
Naples, Napoli, Italy
IRCCS Centro di Riferimento Oncologico
Aviano, Pordenone, Italy
Istituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico Bari
Bari, , Italy
Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)
Bergamo, , Italy
Azienda Sanitaria Ospedaliera S.Croce e Carle
Cuneo, , Italy
IRCCS Ospedale Policlinico San Martino
Genova, , Italy
Ospedale San Raffaele
Milan, , Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, , Italy
IEO Istituto Europeo di Oncologia
Milan, , Italy
IOV - Istituto Oncologico Veneto IRCCS
Padua, , Italy
Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone
Palermo, , Italy
Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia
Perugia, , Italy
Azienda Ospedaliero Universitaria Pisana
Pisa, , Italy
Istituto Nazionale Tumori Regina Elena IRCCS
Roma, , Italy
IDI-Istituto Dermopatico dell'Immacolata IRCCS
Roma, , Italy
Policlinico Universitario di Sassari
Sassari, , Italy
A.O.U. Senese Policlinico Santa Maria alle Scotte
Siena, , Italy
Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino
Torino, , Italy
Azienda Sanitaria Universitaria Friuli Centrale
Udine, , Italy
Antoni van Leeuwenhoek
Amsterdam, , Netherlands
Universitair Medisch Centrum Groningen (UMCG)
Groningen, , Netherlands
Leids Universitair Medisch Centrum
Leiden, , Netherlands
Maastricht University Medical Center
Maastricht, , Netherlands
Radboudumc
Nijmegen, , Netherlands
Erasmus MC
Rotterdam, , Netherlands
UMC Utrecht
Utrecht, , Netherlands
Isala
Zwolle, , Netherlands
Ålesund Hospital
Ålesund, , Norway
Oslo University Hospital
Oslo, , Norway
Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie - Panstwowy Instytut Badawczy
Gliwice, , Poland
Przychodnia Lekarska Komed
Konin, , Poland
Centrum Onkologii-Instytut im. M. Sklodowskiej-Curie
Krakow, , Poland
Wielkopolskie Centrum Onkologii
Poznan, , Poland
Centrum Medyczne Pratia Poznan
Skórzewo, , Poland
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
Warsaw, , Poland
Dolnoslaskie Centrum Onkologii
Wroclaw, , Poland
Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE
Lisbon, , Portugal
Centro Hospitalar de Lisboa Norte, E.P.E. - Hospital de Santa Maria
Lisbon, , Portugal
Instituto Português de Oncologia do Porto Francisco Gentil, EPE
Porto, , Portugal
S.C Medisprof S.R.L
Cluj-Napoca, , Romania
S.C Centrul de Oncologie Sf. Nectarie S.R.L
Craiova, , Romania
Institutul Regional de Oncologie Iasi
Iași, , Romania
Clinical Center "Bezanijska kosa"
Belgrade, , Serbia
Institute of Oncology and Radiology of Serbia
Belgrade, , Serbia
Military Medical Academy
Belgrade, , Serbia
Oncology Institute of Vojvodina
Kamenitz, , Serbia
Clinical Center Kragujevac
Kragujevac, , Serbia
Clinical Center Nis
Niš, , Serbia
National Hospital Oncology
Bloemfontein, Free State, South Africa
Johese Clinical Research: Midstream
Centurion, Gauteng, South Africa
Sandton Oncology Medical Group
Johannesburg, Gauteng, South Africa
ICO Badalona - Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, Spain
ICO l'Hospitalet - Hospital Duran i Reynals
L'Hospitalet de Llobregat, Barcelona, Spain
Hospital Universitario Virgen de la Arrixaca
El Palmar, Murcia, Spain
Hospital Universitari Vall d'Hebron
Barcelona, , Spain
Hospital Clinic de Barcelona
Barcelona, , Spain
Hospital Universitario Reina Sofia
Córdoba, , Spain
Hospital General Universitario Gregorio Marañon
Madrid, , Spain
Hospital Universitario Ramon y Cajal
Madrid, , Spain
Hospital Universitario 12 de Octubre
Madrid, , Spain
Centro Integral Oncologico Clara Campal
Madrid, , Spain
Hospital Regional Universitario de Malaga
Málaga, , Spain
Hospital Clinico Universitario de Valencia
Valencia, , Spain
Hospital General Universitario de Valencia
Valencia, , Spain
Karolinska University Hospital
Stockholm, , Sweden
Norrlands Universitetssjukhus
Umeå, , Sweden
Universitaetsspital Zuerich
Zurich, , Switzerland
Royal Preston Hospital
Preston, Lancashire, United Kingdom
Northern Centre for Cancer Care
Newcastle upon Tyne, Tyne & Wear, United Kingdom
Countries
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References
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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.
Other Identifiers
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W00090GE303/EORTC-2139-MG
Identifier Type: -
Identifier Source: org_study_id