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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

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
Country [10] 0 0
Belgium
State/province [10] 0 0
Brussels
Country [11] 0 0
Belgium
State/province [11] 0 0
Brussel
Country [12] 0 0
Belgium
State/province [12] 0 0
Gent
Country [13] 0 0
Belgium
State/province [13] 0 0
Merksem
Country [14] 0 0
Belgium
State/province [14] 0 0
Sint-Niklaas
Country [15] 0 0
Belgium
State/province [15] 0 0
Yvoir
Country [16] 0 0
Brazil
State/province [16] 0 0
Bahia
Country [17] 0 0
Brazil
State/province [17] 0 0
Paraná
Country [18] 0 0
Brazil
State/province [18] 0 0
Rio Grande Do Sul
Country [19] 0 0
Brazil
State/province [19] 0 0
Santa Catarina
Country [20] 0 0
Brazil
State/province [20] 0 0
Sao Paulo
Country [21] 0 0
Canada
State/province [21] 0 0
Ontario
Country [22] 0 0
Canada
State/province [22] 0 0
Quebec
Country [23] 0 0
Czechia
State/province [23] 0 0
Hradec Králové
Country [24] 0 0
Czechia
State/province [24] 0 0
Olomouc
Country [25] 0 0
Czechia
State/province [25] 0 0
Ostrava - Poruba
Country [26] 0 0
Czechia
State/province [26] 0 0
Praha 10
Country [27] 0 0
Czechia
State/province [27] 0 0
Praha 2
Country [28] 0 0
France
State/province [28] 0 0
Alpes Maritimes
Country [29] 0 0
France
State/province [29] 0 0
Bouches-du-Rhône
Country [30] 0 0
France
State/province [30] 0 0
Cote dÝOr
Country [31] 0 0
France
State/province [31] 0 0
Gironde
Country [32] 0 0
France
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Haute Garonne
Country [33] 0 0
France
State/province [33] 0 0
Hauts De Seine
Country [34] 0 0
France
State/province [34] 0 0
Ille Et Vilaine
Country [35] 0 0
France
State/province [35] 0 0
Indre Et Loire
Country [36] 0 0
France
State/province [36] 0 0
Isere
Country [37] 0 0
France
State/province [37] 0 0
Loire Atlantique
Country [38] 0 0
France
State/province [38] 0 0
Loire
Country [39] 0 0
France
State/province [39] 0 0
Nord
Country [40] 0 0
France
State/province [40] 0 0
Paris
Country [41] 0 0
France
State/province [41] 0 0
Puy De Dome
Country [42] 0 0
France
State/province [42] 0 0
Pyrenees Atlantiques
Country [43] 0 0
France
State/province [43] 0 0
Rhone
Country [44] 0 0
France
State/province [44] 0 0
Seine Maritime
Country [45] 0 0
France
State/province [45] 0 0
Val De Marne
Country [46] 0 0
France
State/province [46] 0 0
Vienne
Country [47] 0 0
Germany
State/province [47] 0 0
Baden Wuerttemberg
Country [48] 0 0
Germany
State/province [48] 0 0
Bayern
Country [49] 0 0
Germany
State/province [49] 0 0
Niedersachsen
Country [50] 0 0
Germany
State/province [50] 0 0
Sachsen
Country [51] 0 0
Germany
State/province [51] 0 0
Schleswig Holstein
Country [52] 0 0
Germany
State/province [52] 0 0
Hamburg
Country [53] 0 0
Greece
State/province [53] 0 0
Athens
Country [54] 0 0
Greece
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Néo Fáliro
Country [55] 0 0
Greece
State/province [55] 0 0
Thessaloníki
Country [56] 0 0
Hungary
State/province [56] 0 0
Budapest
Country [57] 0 0
Hungary
State/province [57] 0 0
Debrecen
Country [58] 0 0
Hungary
State/province [58] 0 0
Gyor
Country [59] 0 0
Hungary
State/province [59] 0 0
Pécs
Country [60] 0 0
Hungary
State/province [60] 0 0
Szeged
Country [61] 0 0
Italy
State/province [61] 0 0
Forli - Cesena
Country [62] 0 0
Italy
State/province [62] 0 0
Messina
Country [63] 0 0
Italy
State/province [63] 0 0
Napoli
Country [64] 0 0
Italy
State/province [64] 0 0
Pordenone
Country [65] 0 0
Italy
State/province [65] 0 0
Bari
Country [66] 0 0
Italy
State/province [66] 0 0
Bergamo
Country [67] 0 0
Italy
State/province [67] 0 0
Cuneo
Country [68] 0 0
Italy
State/province [68] 0 0
Genova
Country [69] 0 0
Italy
State/province [69] 0 0
Milano
Country [70] 0 0
Italy
State/province [70] 0 0
Padova
Country [71] 0 0
Italy
State/province [71] 0 0
Palermo
Country [72] 0 0
Italy
State/province [72] 0 0
Perugia
Country [73] 0 0
Italy
State/province [73] 0 0
Pisa
Country [74] 0 0
Italy
State/province [74] 0 0
Roma
Country [75] 0 0
Italy
State/province [75] 0 0
Sassari
Country [76] 0 0
Italy
State/province [76] 0 0
Siena
Country [77] 0 0
Italy
State/province [77] 0 0
Torino
Country [78] 0 0
Italy
State/province [78] 0 0
Udine
Country [79] 0 0
Netherlands
State/province [79] 0 0
Amsterdam
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Netherlands
State/province [80] 0 0
Groningen
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Netherlands
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Leiden
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Netherlands
State/province [82] 0 0
Maastricht
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Netherlands
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Nijmegen
Country [84] 0 0
Netherlands
State/province [84] 0 0
Rotterdam
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Netherlands
State/province [85] 0 0
Utrecht
Country [86] 0 0
Netherlands
State/province [86] 0 0
Zwolle
Country [87] 0 0
Norway
State/province [87] 0 0
Oslo
Country [88] 0 0
Norway
State/province [88] 0 0
Ålesund
Country [89] 0 0
Poland
State/province [89] 0 0
Gliwice
Country [90] 0 0
Poland
State/province [90] 0 0
Konin
Country [91] 0 0
Poland
State/province [91] 0 0
Kraków
Country [92] 0 0
Poland
State/province [92] 0 0
Poznan
Country [93] 0 0
Poland
State/province [93] 0 0
Skórzewo
Country [94] 0 0
Poland
State/province [94] 0 0
Warszawa
Country [95] 0 0
Poland
State/province [95] 0 0
Wroclaw
Country [96] 0 0
Portugal
State/province [96] 0 0
Lisboa
Country [97] 0 0
Portugal
State/province [97] 0 0
Porto
Country [98] 0 0
Romania
State/province [98] 0 0
Cluj-Napoca
Country [99] 0 0
Romania
State/province [99] 0 0
Craiova
Country [100] 0 0
Romania
State/province [100] 0 0
Iasi
Country [101] 0 0
Serbia
State/province [101] 0 0
Belgrade
Country [102] 0 0
Serbia
State/province [102] 0 0
Kragujevac
Country [103] 0 0
Serbia
State/province [103] 0 0
Niš
Country [104] 0 0
Serbia
State/province [104] 0 0
Sremska Kamenica
Country [105] 0 0
South Africa
State/province [105] 0 0
Free State
Country [106] 0 0
South Africa
State/province [106] 0 0
Gauteng
Country [107] 0 0
Spain
State/province [107] 0 0
Barcelona
Country [108] 0 0
Spain
State/province [108] 0 0
Murcia
Country [109] 0 0
Spain
State/province [109] 0 0
Córdoba
Country [110] 0 0
Spain
State/province [110] 0 0
Madrid
Country [111] 0 0
Spain
State/province [111] 0 0
Málaga
Country [112] 0 0
Spain
State/province [112] 0 0
Valencia
Country [113] 0 0
Sweden
State/province [113] 0 0
Stockholm
Country [114] 0 0
Sweden
State/province [114] 0 0
Umeå
Country [115] 0 0
Switzerland
State/province [115] 0 0
Zuerich
Country [116] 0 0
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
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.

Supporting document/s available: Study protocol, Informed consent form (ICF)
When will data be available (start and end dates)?
* 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.
Available to whom?
Pierre Fabre corporate portal
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05270044