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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05270044




Registration number
NCT05270044
Ethics application status
Date submitted
14/02/2022
Date registered
8/03/2022
Date last updated
22/11/2023

Titles & IDs
Public title
Adjuvant Encorafenib and Binimetinib in High-risk Stage II Melanoma With a BRAF Mutation.
Scientific 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
Secondary ID [1] 0 0
W00090GE303/EORTC-2139-MG
Universal Trial Number (UTN)
Trial acronym
COLUMBUS-AD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Encorafenib and Binimetinib
Treatment: Drugs - Placebo to match Encorafenib ; Placebo to match Binimetinib

Experimental: Arm A - Encorafenib and Binimetinib

Placebo comparator: Arm B - Placebo to match Encorafenib Placebo to match Binimetinib


Treatment: Drugs: 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.

Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Recurrence-free survival (RFS)
Timepoint [1] 0 0
Approximately 4.4 years from the accrual of the first patient.
Secondary outcome [1] 0 0
Distant metastasis-free survival (DMFS)
Timepoint [1] 0 0
Approximately 6.0 years from first patient in
Secondary outcome [2] 0 0
Overall survival (OS)
Timepoint [2] 0 0
Approximately 10 years from first Patient In.
Secondary outcome [3] 0 0
Safety - Incidence, nature, severity and seriousness of treatment emergent adverse events (TEAEs)
Timepoint [3] 0 0
From the signing of the ICF up to 30 days after end of treatment- approximately 14.5 months
Secondary outcome [4] 0 0
Safety -Incidence, nature and severity of cutaneous malignancies by dermatological examination
Timepoint [4] 0 0
From the signing of ICF to study completion- approximately 10 years from last patient in
Secondary outcome [5] 0 0
Safety -Incidence of Serious adverse events (SAEs)
Timepoint [5] 0 0
From the signing of the ICF to study completion- approximately 10 years from last patient in
Secondary outcome [6] 0 0
Safety and tolerability - Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes in physical examination
Timepoint [6] 0 0
From the signing of the ICF up to 30 days after end of treatment- approximately up to 14.5 months
Secondary outcome [7] 0 0
Safety and tolerability - Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes in vital signs
Timepoint [7] 0 0
From the signing of the ICF up to 30 days after end of treatment- approximately up to 14.5 months
Secondary outcome [8] 0 0
Safety and tolerability : Incidence of TEAEs related to notable changes in clinical safety laboratory parameters from baseline.
Timepoint [8] 0 0
From the signing of the ICF up to 30 days after end of treatment- approximately up to 14.5 months
Secondary outcome [9] 0 0
Safety and tolerability -Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes from baseline of 12-lead electrocardiograms (ECGs)
Timepoint [9] 0 0
From the signing of the ICF up to 30 days after end of treatment-approximately up to 14.5 months
Secondary outcome [10] 0 0
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.
Timepoint [10] 0 0
From the signing of the ICF up to 30 days after end of treatment-approximately up to 14.5 months
Secondary outcome [11] 0 0
Safety and tolerability - Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes in ophtalmic examination
Timepoint [11] 0 0
From the signing of the ICF up to 30 days after end of treatment-approximately up to 14.5 months
Secondary outcome [12] 0 0
Safety and tolerability-Treatment emergent adverse events (TEAEs) leading to dose interruption, reduction and discontinuation.
Timepoint [12] 0 0
On treatment period - 12 months from randomization.
Secondary outcome [13] 0 0
Performance status using the Eastern Co-operative Oncology Group (ECOG) performance status scale.
Timepoint [13] 0 0
From the signing of the ICF up to 30 days after end of treatment-approximately up to 14.5 months
Secondary outcome [14] 0 0
Patient-reported health-related (HRQoL)-European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) .
Timepoint [14] 0 0
From the signing of the ICF up to 30 months.
Secondary outcome [15] 0 0
Patient-reported health-related (HRQoL)_European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer Patients (EORTC QLQ-C30)
Timepoint [15] 0 0
From the signing of the ICF up to 30 months.
Secondary outcome [16] 0 0
Pharmacokinetic (PK) parameter of encorafenib and its metabolite (LHY746)_Cmin
Timepoint [16] 0 0
From randomization up to 11 months
Secondary outcome [17] 0 0
Pharmacokinetic (PK) parameter of encorafenib and its metabolite (LHY746)-Cmax
Timepoint [17] 0 0
From randomization up to 11 months
Secondary outcome [18] 0 0
Pharmacokinetic (PK) parameter of encorafenib and its metabolite (LHY746)_AUC
Timepoint [18] 0 0
From randomization up to 11 months
Secondary outcome [19] 0 0
Pharmacokinetic (PK) parameter of binimetinib and its metabolite (AR00426032)-Cmin
Timepoint [19] 0 0
From randomization up to 11 months
Secondary outcome [20] 0 0
Pharmacokinetic (PK) parameter of binimetinib and its metabolite (AR00426032)-Cmax
Timepoint [20] 0 0
From randomization up to 11 months
Secondary outcome [21] 0 0
Pharmacokinetic (PK) parameter of binimetinib and its metabolite (AR00426032)-AUC
Timepoint [21] 0 0
From randomization up to 11 months

Eligibility
Key inclusion criteria
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;
* 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 ß-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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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;
* 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/05/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
2/05/2035
Actual
Sample size
Target
815
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Westmead Hospital - Sydney
Recruitment hospital [2] 0 0
Melanoma Institute Australia - Wollstonecraft
Recruitment hospital [3] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [4] 0 0
Adelaide Oncology & Haematolog, Calvary North Adelaide Hospital - North Adelaide
Recruitment hospital [5] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [6] 0 0
Austin Health - Heidelberg
Recruitment hospital [7] 0 0
The Alfred Hospital - Prahran
Recruitment hospital [8] 0 0
Hollywood Private Hospital - Nedlands
Recruitment hospital [9] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
2145 - Sydney
Recruitment postcode(s) [2] 0 0
2065 - Wollstonecraft
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [4] 0 0
5006 - North Adelaide
Recruitment postcode(s) [5] 0 0
3128 - Box Hill
Recruitment postcode(s) [6] 0 0
3084 - Heidelberg
Recruitment postcode(s) [7] 0 0
3181 - Prahran
Recruitment postcode(s) [8] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
Argentina
State/province [1] 0 0
Buenos Aires
Country [2] 0 0
Argentina
State/province [2] 0 0
Ciudad Autonoma Buenos Aires
Country [3] 0 0
Argentina
State/province [3] 0 0
Santa Fe
Country [4] 0 0
Austria
State/province [4] 0 0
Graz
Country [5] 0 0
Austria
State/province [5] 0 0
Linz
Country [6] 0 0
Austria
State/province [6] 0 0
St. Pölten
Country [7] 0 0
Austria
State/province [7] 0 0
Vienna
Country [8] 0 0
Belgium
State/province [8] 0 0
Anderlecht
Country [9] 0 0
Belgium
State/province [9] 0 0
Antwerpen
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Belgium
State/province [10] 0 0
Brussels
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Belgium
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Brussel
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Belgium
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Gent
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Belgium
State/province [13] 0 0
Merksem
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Belgium
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Sint-Niklaas
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Belgium
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Yvoir
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Brazil
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Bahia
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Brazil
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Paraná
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Brazil
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Rio Grande Do Sul
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Santa Catarina
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Sao Paulo
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Ontario
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Quebec
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Czechia
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Hradec Králové
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Olomouc
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Ostrava - Poruba
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Czechia
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Praha 10
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Czechia
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Praha 2
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Alpes Maritimes
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Isere
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Vienne
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Baden Wuerttemberg
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Bayern
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Germany
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Niedersachsen
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Germany
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Sachsen
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Germany
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Schleswig Holstein
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Hamburg
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Greece
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Athens
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Budapest
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Debrecen
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Gyor
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Hungary
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Pécs
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Hungary
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Szeged
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Italy
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Forli - Cesena
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Messina
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Napoli
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Pordenone
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Bari
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Bergamo
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Cuneo
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Genova
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Milano
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Padova
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Palermo
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Perugia
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Pisa
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Roma
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Sassari
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Siena
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Torino
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Udine
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Amsterdam
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Leiden
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Maastricht
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Nijmegen
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Rotterdam
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Utrecht
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Netherlands
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Zwolle
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Norway
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Oslo
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Norway
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Ålesund
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Poland
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Gliwice
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Poland
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Konin
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Kraków
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Poznan
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Poland
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Skórzewo
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Warszawa
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Wroclaw
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Portugal
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Lisboa
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Portugal
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Porto
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Romania
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Cluj-Napoca
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Romania
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Craiova
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Romania
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Iasi
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Serbia
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Belgrade
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Serbia
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Kragujevac
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Serbia
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Niš
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Serbia
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Sremska Kamenica
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South Africa
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Free State
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South Africa
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Gauteng
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Spain
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Barcelona
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Murcia
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Córdoba
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Madrid
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Spain
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Málaga
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Spain
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Valencia
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Sweden
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Stockholm
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Sweden
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Umeå
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Switzerland
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Zuerich
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United Kingdom
State/province [116] 0 0
Lancashire
Country [117] 0 0
United Kingdom
State/province [117] 0 0
Tyne & Wear

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pierre Fabre Medicament
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
European Organisation for Research and Treatment of Cancer - EORTC
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/study/NCT05270044
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Alexander C.J. van AKKOOI, MD, PhD
Address 0 0
European Organisation for Research and Treatment of Cancer - EORTC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05270044