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

Study Purpose

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).

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

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 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:

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.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05270044
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 3
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Pierre Fabre Medicament
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Alexander C.J. van AKKOOI, MD, PhD
Principal Investigator Affiliation	European Organisation for Research and Treatment of Cancer - EORTC
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry, Other
Overall Status	Recruiting
Countries	Argentina, Australia, Austria, Belgium, Brazil, Canada, Czechia, France, Germany, Greece, Hungary, Israel, Italy, Netherlands, Norway, Poland, Portugal, Serbia, South Africa, Spain, Sweden, Switzerland, United Kingdom
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Melanoma

Additional Details

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.

Arms & Interventions

Arms

Experimental: Arm A

Encorafenib and Binimetinib

Placebo Comparator: Arm B

Placebo to match Encorafenib Placebo to match Binimetinib

Interventions

Drug: - 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.

Drug: - 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.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Centro Oncologico Korben, Caba, Buenos Aires, Argentina

Status

Not yet recruiting

Address

Centro Oncologico Korben

Caba, Buenos Aires, C1426

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