AzTrials
AzTrials

MelanomaPhase 3COLUMBUS-ADNCT05270044

Adjuvant Encorafenib and Binimetinib in High-risk Stage II Melanoma With a BRAF Mutation.

A Phase 3 study testing Encorafenib and Binimetinib in people with Melanoma, run by Pierre Fabre Medicament at 155 sites in 23 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Melanoma
What is being tested?
Encorafenib and Binimetinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
815 participants
Where
155 sitesin 23 countries
Study dates
2 May 2022to 2 May 2035
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • Pre-screening
  • Unknown ulceration status;
  • Uveal and mucosal melanoma;
  • Clinically apparent metastases (N+/M1);
  • Microsatellites, satellites and/or in-transit metastases,
  • Local (scar) recurrences.
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  • 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.

Trial locations and contacts

155 sites in 23 countries.

155 sites in 23 countries

Italy21 sites

  • IRCCS Centro di Riferimento Oncologico

    Aviano, Pordenone, 33081

  • Istituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico Bari

    Bari, 70124

  • Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)

    Bergamo, 24127

  • Azienda Sanitaria Ospedaliera S.Croce e Carle

    Cuneo, 12100

  • IRCCS Ospedale Policlinico San Martino

    Genova, 16132

  • IRCCS Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori "Dino Amadori" - IRST

    Meldola, Forli - Cesena, 47014

  • Ospedale San Raffaele

    Milan, 20132

  • Fondazione IRCCS Istituto Nazionale dei Tumori

    Milan, 20133

  • IEO Istituto Europeo di Oncologia

    Milan, 20141

  • Istituto Nazionale Tumori Fondazione G. Pascale

    Naples, Napoli, 80131

  • IOV - Istituto Oncologico Veneto IRCCS

    Padova, 35128

  • Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone

    Palermo, 90127

  • Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia

    Perugia, 06156

  • Azienda Ospedaliero Universitaria Pisana

    Pisa, 56126

  • Istituto Nazionale Tumori Regina Elena IRCCS

    Roma, 00144

  • IDI-Istituto Dermopatico dell'Immacolata IRCCS

    Roma, 00167

  • Policlinico Universitario di Sassari

    Sassari, 07100

  • A.O.U. Senese Policlinico Santa Maria alle Scotte

    Siena, 53100

  • Ospedale San Vincenzo

    Taormina, Messina, 98039

  • Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino

    Torino, 10126

  • Azienda Sanitaria Universitaria Friuli Centrale

    Udine, 33100

Other trials in Italy

France19 sites

  • CHU de Bordeaux - Hôpital Saint André

    Bordeaux, Gironde, 33075

  • Hôpital Ambroise Paré

    Boulogne-Billancourt, Hauts De Seine, 92100

  • CHU Tours - Hôpital Trousseau

    Chambray-lès-Tours, Indre Et Loire, 37170

  • CAC Clermont-Ferrand Centre Jean Perrin

    Clermont-Ferrand, Puy De Dome, 63000

  • CHU de Dijon - Hôpital du Bocage

    Dijon, Cote dÝOr, 21079

  • CHU de Grenoble - Hôpital André Michallon

    La Tronche, Isere, 38700

  • Hopital Claude Huriez - CHU Lille

    Lille, Nord, 59037

  • Hôpital de la Timone

    Marseille, Bouches-du-Rhône, 13385

  • CHU Nantes - Hôtel Dieu

    Nantes, Loire Atlantique, 44093

  • CHU Nice - Hopital de l Archet 2

    Nice, Alpes Maritimes, 06202

  • Hôpital Saint-Louis

    Paris, Paris, 75010

  • Centre Hospitalier de Pau - Hôpital François Mitterrand

    Pau, Pyrenees Atlantiques, 64046

  • Centre Hospitalier Lyon Sud

    Pierre-Bénite, Rhone, 69495

  • CHU Poitiers - Hôpital la Milétrie

    Poitiers, Vienne, 86021

  • CRLCC Eugene Marquis

    Rennes, Ille Et Vilaine, 35042

  • CHU de Rouen - Hôpital Charles Nicolle

    Rouen, Seine Maritime, 76031

  • CHU Saint Etienne - Hôpital Nord

    Saint-Étienne-de-Montluc, Pays de la Loire Region, 42055

  • Institut Claudius Regaud - Oncopole

    Toulouse, Haute Garonne, 31059

  • Institut Gustave Roussy

    Villejuif, Val De Marne, 94805

Other trials in France

Spain13 sites

  • ICO Badalona - Hospital Universitari Germans Trias i Pujol

    Badalona, Barcelona, 08916

  • Hospital Universitari Vall d'Hebron

    Barcelona, 08035

  • Hospital Clinic de Barcelona

    Barcelona, 08036

  • Hospital Universitario Reina Sofia

    Córdoba, 14004

  • Hospital Universitario Virgen de la Arrixaca

    El Palmar, Murcia, 30120

  • ICO l'Hospitalet - Hospital Duran i Reynals

    L'Hospitalet de Llobregat, Barcelona, 08908

  • Hospital General Universitario Gregorio Marañon

    Madrid, 28007

  • Hospital Universitario Ramon y Cajal

    Madrid, 28034

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Centro Integral Oncologico Clara Campal

    Madrid, 28050

  • Hospital Regional Universitario de Malaga

    Málaga, 29010

  • Hospital Clinico Universitario de Valencia

    Valencia, 46010

  • Hospital General Universitario de Valencia

    Valencia, 46014

Other trials in Spain

Brazil10 sites

  • Hospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer

    Curitiba, Paraná, 81520-060

  • CEPON - Centro de Pesquisas Oncológicas de Santa Catarina

    Florianópolis, Santa Catarina, 88034-000

  • Fundação Doutor Amaral Carvalho

    Jaú, São Paulo, 17210-120

  • Instituto de Cancer de Londrina

    Londrina, Paraná, 86015-520

  • Hospital de Clínicas de Porto Alegre

    Porto Alegre, Rio Grande do Sul, 90035-903

  • HGB - Hospital Giovanni Battista - Mãe de Deus Center

    Porto Alegre, Rio Grande do Sul, 90110-270

  • AMO - Assistência Multidisciplinar em Oncologia

    Salvador, Estado de Bahia, 41950-640

  • Instituto de Oncologia Saint Gallen

    Santa Cruz do Sul, Rio Grande do Sul, 96810-110

  • CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia

    Santo André, São Paulo, 09060-870

  • A. C. Camargo Cancer Center

    São Paulo, São Paulo, 01509-900

Other trials in Brazil

Australia9 sites

  • Box Hill Hospital

    Box Hill, Victoria, 3128

  • Austin Health

    Heidelberg, Victoria, 3084

  • Hollywood Private Hospital

    Nedlands, Western Australia, 6009

  • Sir Charles Gairdner Hospital

    Nedlands, Western Australia, 6009

  • Adelaide Oncology & Haematolog, Calvary North Adelaide Hospital

    North Adelaide, South Australia, 5006

  • The Alfred Hospital

    Prahran, Victoria, 3181

  • Westmead Hospital

    Sydney, New South Wales, 2145

  • Melanoma Institute Australia

    Wollstonecraft, New South Wales, 2065

  • Princess Alexandra Hospital

    Woolloongabba, Queensland, 4102

Other trials in Australia

Argentina8 sites

  • Centro Oncologico Korben

    CABA, Buenos Aires, C1426

  • Fundacion CIDEA

    Ciudad Autonoma Bs As, Ciudad Autonoma Buenos Aires, C1121ABE

  • Hospital Aleman

    Ciudad Autonoma Buenos Aires, C1118AAT

  • Instituto Medico Especializado Alexander Fleming

    Ciudad Autonoma Buenos Aires, C1426ANZ

  • Clinica Adventista Belgrano

    Ciudad Autonoma Buenos Aires, C1430EGF

  • Centro de Investigaciones Medicas Mar del Plata

    Mar del Plata, Buenos Aires, B7600FYK

  • Sanatorio Britanico S.A.

    Rosario, Santa Fe Province, 2000

  • Instituto de Oncologia de Rosario

    Rosario, Santa Fe Province, S2000KZE

Other trials in Argentina

Belgium8 sites

  • Institut Jules Bordet

    Anderlecht, 1070

  • ZNA Middelheim

    Antwerp, 2020

  • Universitair Ziekenhuis Brussel

    Brussels, 1090

  • Cliniques Universitaires Saint-Luc

    Brussels, 1200

  • UZ Gent

    Ghent, 9000

  • ZNA

    Merksem, 2170

  • Vitaz

    Sint-Niklaas, 9100

  • CHU UCL Namur

    Yvoir, 5530

Other trials in Belgium

Netherlands8 sites

  • Antoni van Leeuwenhoek

    Amsterdam, 1066 CX

  • Universitair Medisch Centrum Groningen (UMCG)

    Groningen, 9713 GZ

  • Leids Universitair Medisch Centrum

    Leiden, 2333 ZA

  • Maastricht University Medical Center

    Maastricht, 6202 AZ

  • Radboudumc

    Nijmegen, 6525 GA

  • Erasmus MC

    Rotterdam, 3015 GD

  • UMC Utrecht

    Utrecht, 3508 GA

  • Isala

    Zwolle, 8025 AB

Other trials in Netherlands

Poland7 sites

  • Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie - Panstwowy Instytut Badawczy

    Gliwice, 44-102

  • Przychodnia Lekarska Komed

    Konin, 62-500

  • Centrum Onkologii-Instytut im. M. Sklodowskiej-Curie

    Krakow, 31-115

  • Wielkopolskie Centrum Onkologii

    Poznan, 61-866

  • Centrum Medyczne Pratia Poznan

    Skórzewo, 60-185

  • Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy

    Warsaw, 02-781

  • Dolnoslaskie Centrum Onkologii

    Wroclaw, 53-413

Other trials in Poland

Germany6 sites

  • Elbekliniken Buxtehude GmbH

    Buxtehude, Lower Saxony, 21614

  • Universitaetsklinikum Carl Gustav Carus TU Dresden

    Dresden, Saxony, 01307

  • Universitaetsklinikum Hamburg-Eppendorf

    Hamburg, 20246

  • Universitaetsklinikum Heidelberg

    Heidelberg, Baden-Wurttemberg, 69120

  • Universitaetsklinikum Schleswig-Holstein

    Kiel, Schleswig-Holstein, 24105

  • Universitaetsklinikum Wuerzburg

    Würzburg, Bavaria, 97080

Other trials in Germany

Hungary6 sites

  • Semmelweis Egyetem

    Budapest, 1085

  • Orszagos Onkologiai Intezet

    Budapest, 1122

  • Debreceni Egyetem

    Debrecen, 4032

  • Petz Aladar Egyetemi Oktato Korhaz

    Győr, 9023

  • Pecsi Tudomanyegyetem

    Pécs, 7632

  • Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont

    Szeged, 6720

Other trials in Hungary

Serbia6 sites

  • Clinical Center "Bezanijska kosa"

    Belgrade, 11000

  • Institute of Oncology and Radiology of Serbia

    Belgrade, 11000

  • Military Medical Academy

    Belgrade, 11000

  • Oncology Institute of Vojvodina

    Kamenitz, 21204

  • Clinical Center Kragujevac

    Kragujevac, 34000

  • Clinical Center Nis

    Niš, 18000

Other trials in Serbia

Czechia5 sites

  • Fakultni nemocnice Hradec Kralove

    Hradec Králové, 500 05

  • Fakultni nemocnice Olomouc

    Olomouc, 79900

  • Fakultni nemocnice Ostrava

    Ostrava - Poruba, 708 52

  • Fakultni nemocnice Kralovske Vinohrady

    Prague, 100 34

  • Vseobecna fakultni nemocnice v Praze

    Prague, 128 08

Other trials in Czechia

Greece5 sites

  • General Hospital of Athens Laiko

    Athens, 11527

  • Metropolitan Hospital

    Neo Faliro, 18547

  • Bioclinic Thessaloniki

    Thessaloniki, 54622

  • Anticancer Hospital of Thessaloniki " Theagenio"

    Thessaloniki, 54639

  • Interbalkan Hospital of Thessaloniki

    Thessaloniki, 57001

Other trials in Greece

Austria4 sites

  • Landeskrankenhaus - Universitaetsklinikum Graz

    Graz, 8036

  • Krankenhaus der Elisabethinen Linz

    Linz, 4020

  • Universitätsklinikum St.Pölten-Lilienfeld

    Sankt Pölten, 3100

  • AKH - Medizinische Universität Wien

    Vienna, 1090

Other trials in Austria

Canada4 sites

  • London Health Sciences Centre (LHSC) - Victoria Hospital

    London, Ontario, N6A 5W9

  • CIUSSS du Centre Ouest de l'lle de Montreal

    Montreal, Quebec, H3T 1E2

  • Toronto Sunnybrook Hospital

    Toronto, Ontario, M4N 3M5

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 2M9

Other trials in Canada

Portugal3 sites

  • Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE

    Lisbon, 1099-023

  • Centro Hospitalar de Lisboa Norte, E.P.E. - Hospital de Santa Maria

    Lisbon, 1649-035

  • Instituto Português de Oncologia do Porto Francisco Gentil, EPE

    Porto, 4200-072

Other trials in Portugal

Romania3 sites

  • S.C Medisprof S.R.L

    Cluj-Napoca, 400641

  • S.C Centrul de Oncologie Sf. Nectarie S.R.L

    Craiova, 200542

  • Institutul Regional de Oncologie Iasi

    Iași, 700483

Other trials in Romania

South Africa3 sites

  • National Hospital Oncology

    Bloemfontein, Free State, 9301

  • Johese Clinical Research: Midstream

    Centurion, Gauteng, 1692

  • Sandton Oncology Medical Group

    Johannesburg, Gauteng, 2196

Other trials in South Africa

Norway2 sites

  • Ålesund Hospital

    Ålesund, 6017

  • Oslo University Hospital

    Oslo, 0424

Other trials in Norway

Sweden2 sites

  • Karolinska University Hospital

    Stockholm, 17176

  • Norrlands Universitetssjukhus

    Umeå, 901 87

Other trials in Sweden

United Kingdom2 sites

  • Northern Centre for Cancer Care

    Newcastle upon Tyne, Tyne & Wear, NE7 7DN

  • Royal Preston Hospital

    Preston, Lancashire, PR2 9HT

Other trials in United Kingdom

Switzerland1 site

  • Universitaetsspital Zuerich

    Zurich, 8091

Other trials in Switzerland

About this study

Official title: 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

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).

Read the detailed description

This is a randomized triple-blind placebo-controlled international multicenter phase III superiority clinical trial.

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
Melanoma
Being tested
Encorafenib and Binimetinib, Placebo to match Encorafenib ; Placebo to match Binimetinib
Keywords
Melanoma, Stage II, BRAFV600E/K, Adjuvant
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Encorafenib and BinimetinibDrug

    Also called Encorafenib: Braftovi / Binimetinib: Mektovi

    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 BinimetinibDrug

    Encorafenib (6 × 75 mg placebo capsules) QD and binimetinib (3 × 15 mg placebo tablets) BID placebos orally for a maximum of 12 months.

Study groups in NCT05270044
Study groupRoleWhat they receive
Arm AExperimentalEncorafenib and Binimetinib
Receives: Drug: Encorafenib and Binimetinib
Arm BPlacebo comparatorPlacebo to match Encorafenib Placebo to match Binimetinib
Receives: Drug: Placebo to match Encorafenib ; Placebo to match Binimetinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Approximately 4.4 years from the accrual of the first patient.

Secondary outcomes (21)

  1. Distant metastasis-free survival (DMFS)

    DMFS is defined as the time between the date of randomization and the date of first distant metastasis or date of death (whatever the cause), whichever occurs first.

    Measured: Approximately 6.0 years from first patient in

  2. Overall survival (OS)

    OS is defined as time from randomization to the date of death whatever the cause.

    Measured: Approximately 10 years from first Patient In.

  3. Safety - Incidence, nature, severity and seriousness of treatment emergent adverse events (TEAEs)

    Incidence nature and severity of adverse events and SAEs graded as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0

    Measured: From the signing of the ICF up to 30 days after end of treatment- approximately 14.5 months

  4. Safety -Incidence, nature and severity of cutaneous malignancies by dermatological examination

    This is to monitor for the possible development of keratoacanthoma and/or squamous cell carcinoma and new primary melanoma, as these have been reported to occur with selective BRAF inhibitor treatment. Incidence, nature and severity of new cutaneous malignancies (kerantoacanthoma, squamous cell carcinoma and new primary melanoma) will be recorded and graded as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0

    Measured: From the signing of ICF to study completion- approximately 10 years from last patient in

  5. Safety -Incidence of Serious adverse events (SAEs)

    Incidence nature and severity of serious adverse events will be recorded and graded as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0

    Measured: From the signing of the ICF to study completion- approximately 10 years from last patient in

  6. Safety and tolerability - Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes in physical examination

    Standard physical examinations on cardiovascular, respiratory, gastrointestinal, dermatological, ophthalmological and neurological systems will be performed and will be evaluated based on normal/abnormal and clinical significance observations. Number of participants with TEAEs related to abnormal or clinical significance observations to the physical examinations after the start of study drug will be reported.

    Measured: From the signing of the ICF up to 30 days after end of treatment- approximately up to 14.5 months

  7. Safety and tolerability - Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes in vital signs

    Clinically notable elevated values: Systolic blood pressure (BP): ≥ 160 mmHg and an increase ≥ 20 mmHg from baseline; Diastolic BP: ≥ 100 mmHg and an increase ≥ 15 mmHg from baseline; Heart rate: ≥ 100 beats/min (bpm) with increase from baseline of ≥ 15 bpm; Body temperature [°C] ≥ 38°C). Clinically notable low values: Systolic BP: <120 mmHg with decrease from baseline of ≥ 20 mmHg; Diastolic BP: < 80 mmHg with decrease from baseline of ≥ 15 mmHg; Heart rate: <50 bpm with decrease from baseline of ≥ 15 bpm; Body temperature [°C]: ≤ 35 °C

    Measured: From the signing of the ICF up to 30 days after end of treatment- approximately up to 14.5 months

  8. Safety and tolerability : Incidence of TEAEs related to notable changes in clinical safety laboratory parameters from baseline.

    incidence of treatment-emergent adverse events (TEAEs) related to notable changes in clinical safety laboratory parameters from baseline.

    Number of participants with clinically notable shift from baseline in laboratory parameter values based on national cancer institute common terminology criteria (NCI-CTCAE) grade, Version 5.0 will be graded from Grades 1 to 5. Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death. Clinically notable shift is defined as a worsening from baseline by at least 2 grades, or to grade 3 or above.

    Measured: From the signing of the ICF up to 30 days after end of treatment- approximately up to 14.5 months

  9. Safety and tolerability -Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes from baseline of 12-lead electrocardiograms (ECGs)

    12-lead ECGs will be obtained using an internationally recognized 12-lead cardiograph. Clinically notable ECG values: QT [millisecond (ms)] and QT interval (ms) corrected for heart rate using Fridericia's formula (QTcF) intervals (ms): increase from baseline > 60 ms, new > 450 ms, new > 480 ms, new > 500 ms.

    Measured: From the signing of the ICF up to 30 days after end of treatment-approximately up to 14.5 months

  10. Safety and tolerability - Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes from baseline of echocardiogram or multigated acquisition (ECHO/MUGA) scans.

    ECHO/MUGA scan assess Left Ventricular Ejection Fraction (LVEF). Changes from baseline of LVEF measurements over time will be reported

    Measured: From the signing of the ICF up to 30 days after end of treatment-approximately up to 14.5 months

  11. Safety and tolerability - Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes in ophtalmic examination

    Changes from baseline and worse value on ophthalmic examination over time will be reported.

    a full ophthalmic examination by an ophthalmologist will be performed (at baseline an end of treatment) including best corrected visual acuity (BCVA), slit lamp examination, intraocular pressure (IOP), dilatedfundoscopy and optical coherence tomography (OCT). Retinal examination is required to identify findings associated with retinal pigment epithelial detachments (RPED), serous detachment of the retina and RVO (OCT and angiography).

    the investigator will also monthly monitor visual assesment (general inspection of the eyes, examination of motility and alignment, visual disturbance including diminished central vision, blurred vision or loss of vision).

    Measured: From the signing of the ICF up to 30 days after end of treatment-approximately up to 14.5 months

  12. Safety and tolerability-Treatment emergent adverse events (TEAEs) leading to dose interruption, reduction and discontinuation.

    Incidence of dose interruptions, dose modifications and discontinuation due to AEs and incidence of AEs requiring additional therapy

    Measured: On treatment period - 12 months from randomization.

  13. Performance status using the Eastern Co-operative Oncology Group (ECOG) performance status scale.

    Changes from baseline and worse value on Eastern Cooperative Oncology Group (ECOG) Scale with a range from 0 to 5 with lower score mean a lower functional impairment, 5 corresponding to death .

    Measured: From the signing of the ICF up to 30 days after end of treatment-approximately up to 14.5 months

  14. Patient-reported health-related (HRQoL)-European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) .

    To determine if there is any change from baseline during the treatment and every 6 months thereafter up to 30 months in the European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) questionnaire scores.

    EQ-5D-5L consists of the EQ-5D descriptive system and the EQ visual analogue scale (VAS). The descriptive system has five dimension (mobility, self-care, usual activities, pain/discomfort and anxiety/depression), each is rated according to a five-point verbal rating scale (VRS): 1. no problems, 2. slight problems, 3. moderate problems, 4. severe problems and 5. extreme problems) and translated into a five-digit number that describes the participant's health state

    Measured: From the signing of the ICF up to 30 months.

  15. Patient-reported health-related (HRQoL)_European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer Patients (EORTC QLQ-C30)

    To determine if there is any change from baseline during the treatment and every 6 months thereafter up to 30 months in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer Patients (EORTC QLQ-C30) questionnaire scores EORTC QLQ-C30 consists of fifteen multi-item scales: five functional scales (physical, role, cognitive, emotional and social); nine symptom/items scales (fatigue, pain, nausea, vomiting, dyspnea, insomnia, apetite loss, constipation, diarrhae and financial difficulties) and a global health and Quality of Life (QoL) scale. Each scale in the questionnaire will be scored (0 to 100). High scores represents a high health/quality of life

    Measured: From the signing of the ICF up to 30 months.

  16. Pharmacokinetic (PK) parameter of encorafenib and its metabolite (LHY746)_Cmin

    Minimum serum concentration (Cmin) will be calculated and reported.

    Measured: From randomization up to 11 months

  17. Pharmacokinetic (PK) parameter of encorafenib and its metabolite (LHY746)-Cmax

    Maximum serum concentration (Cmax) will be calculated and reported.

    Measured: From randomization up to 11 months

  18. Pharmacokinetic (PK) parameter of encorafenib and its metabolite (LHY746)_AUC

    Area under the curve (AUC) will be calculated and reported.

    Measured: From randomization up to 11 months

  19. Pharmacokinetic (PK) parameter of binimetinib and its metabolite (AR00426032)-Cmin

    Minimum serum concentration (Cmin) will be calculated and reported

    Measured: From randomization up to 11 months

  20. Pharmacokinetic (PK) parameter of binimetinib and its metabolite (AR00426032)-Cmax

    Maximum serum concentration (Cmax) will be calculated and reported.

    Measured: From randomization up to 11 months

  21. Pharmacokinetic (PK) parameter of binimetinib and its metabolite (AR00426032)-AUC

    Area under the curve (AUC) will be calculated and reported.

    Measured: From randomization up to 11 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Mar 2022
  2. Study start2 May 2022
  3. Primary completion31 Mar 2027 (estimated)
  4. Study completion2 May 2035 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
815 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05270044
Sponsor's protocol ID
W00090GE303/EORTC-2139-MG
Acronym
COLUMBUS-AD
Status last verified
Nov 2023
First submitted
14 Feb 2022
Last updated
22 Nov 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • 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.

    PubMed 37665297

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Encorafenib and Binimetinib in people with Melanoma, run by Pierre Fabre Medicament at 155 sites in 23 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 22 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 155 sites in Italy, France, Spain, Brazil, Australia and 18 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recurrence-free survival (RFS) (time frame: Approximately 4.4 years from the accrual of the first patient.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05270044, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2023.

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