Resected BRAF V600E/K stage II melanoma MedDRA version: 21.1 Level: LLT Classification code 10053571 Term: Melanoma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Braftovi
Product Name: Encorafenib
Product Code: [W0090]
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: ENCORAFENIB
CAS Number: 1269440-17-6
Current Sponsor code: W0090
Concentrat
Sponsors
PIERRE FABRE MéDICAMENT
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Molecular pre-screening 1. Before any related study activity, written informed consent must be given according to ICH/GCP, and national/local regulations ; 2. Male or female = 18 years of age; 3. Surgically resected, with tumor free margins, and histologically/pathologically confirmed new diagnosis of stage II (pT2bpT4bN0) cutaneous melanoma per AJCC 8th edition; 4. Sentinel node (SN) staged node negative (pN0); 5. Sentinel node (SN) biopsy within 14 weeks from initial diagnosis of melanoma; Screening 1. Melanoma determined locally to be V600E/K mutation-positive. Note: only PCR and NGS-based local assay results will be acceptable; 2. Participant still free of disease as evidenced by the required baseline imaging and physical/dermatological assessments performed within 6 weeks from the randomization (Day 1); 3. Before any related study activity, written informed consent must be given according to ICH/GCP, and national/local regulations; 4. Randomization within 12 weeks from SN biopsy; 5. Able to provide a sufficient amount of representative tumor specimen (diagnostic biopsy) for retrospective central testing of BRAFV600E/K mutation status. FFPE tumor tissue block or a minimum of 10 slides, optimally up to 15 slides; 6. Recovered from definitive surgery (e.g. complete wound healing, no uncontrolled wound infections or indwelling drains); 7. ECOG performance status of 0 or 1; 8. Adequate bone marrow function: i. Absolute neutrophil count (ANC) = 1.5 x 1000000000/L ii. Platelets = 100 x1000000000 /L iii. Hemoglobin = 9.0 g/dL 9. Adequate renal function: Serum creatinine = 1.5 × ULN; or calculated creatinine clearance = 50 mL/min by Cockcroft-Gault formula; 10. Adequate electrolytes, defined as serum potassium and magnesium levels within institutional normal limits. 11. Adequate hepatic function: i. Serum total bilirubin = 1.5 x ULN and =65 years) yes F.1.3.1 Number of subjects for this age range 180
Exclusion criteria
Exclusion criteria: Molecular pre-screening 1. Unknown ulceration status; 2. Uveal and mucosal melanoma; 3. Clinically apparent metastases (N+/M1); 4. Microsatellites, satellites and/or in-transit metastases; 5. Local (scar) recurrences. Screening 1. Breast feeding women; 2. History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes); 3. History of thromboembolic or cerebrovascular events = 12 weeks prior to randomization; i. Note 1: Thromboembolic or cerebrovascular events include stroke, transient ischemic attacks, cerebrovascular accidents, hemodynamically significant (i.e massive or sub-massive) deep vein thrombosis, pulmonary emboli, aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis; ii. Note 2: Participants with thromboembolic events related to indwelling catheters or other procedures may be enrolled; 4. Previous or concurrent malignancy for the past 3 years (must be free from disease for at least 3 years). Except for non-melanoma skin cancer (Basal Cell Carcinomas or Squamous Cell Carcinomas) and any in situ cancer; 5.Participants with a prior cancer associated with RAS mutation; 6. Previous treatment for melanoma beyond complete surgical resection (any prior systemic anticancer therapy; prior radiotherapy); 7. Hypersensitivity to the study drugs or to any of the excipients; 8. Participants with severe lactose intolerance (e.g Rare hereditary problems of galactose intolerance, total lactase deficiency or glucosegalactose malabsorption); 9.Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following: iii. History of acute myocardial infarction, acute coronary syndromes (including unstable angina, coronary artery bypass graft, coronary angioplasty or stenting) = 6 months prior to randomization; iv. Congestive heart failure requiring treatment (New York Heart Association Grade = 2); v. Uncontrolled hypertension defined as persistent systolic blood pressure = 150 mmHg or diastolic blood pressure = 100 mmHg despite optimal therapy; vi. Presence of clinically significant cardiac arrhythmias including uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia (stable controlled atrial fibrillation or paroxysmal supraventricular tachycardia is accepted); 10. Neuromuscular disorders that are associated with CK > ULN (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy); 11. Non-infectious pneumonitis and Interstitial Lung Disease; 12. 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; 13. Known history of a positive serology for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS), known history of a positive serology for active hepatitis B, and/or hepatitis C; 14. Unable to ingest or digest tablets and capsules. This can be caused by any impaired gastrointestinal function or disease, such as for example: ulcerative diseases, malabsorption syndrome, small bowel resection, ileus, etc. Or any condition causing uncontrolled nausea, vomiting or diarrhea; 15. Presence of any psychological, familial, sociological or geographical conditions potentially hampering compliance with the study protocol and follow-up s
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To prospectively assess whether treatment with encorafenib and binimetinib prolongs recurrence-free survival as compared to placebo in resected pT2b-4bN0M0 BRAF V600E/K melanoma participants.;Secondary Objective: 1.To prospectively assess whether treatment with encorafenib and binimetinib prolongs distant metastasis-free survival (DMFS) as compared to placebo. 2.To prospectively assess whether treatment with encorafenib and binimetinib prolongs overall survival (OS) as compared to placebo. 3.To characterize the safety and tolerability. 4.To compare the patient-reported health-related (HRQoL) between the two arms during the treatment duration and after treatment completion.;Primary end point(s): Recurrence-free survival (RFS);Timepoint(s) of evaluation of this end point: Approximately 4.7 years from the accrual of the first patient.The longterm evaluation will take place 10 years from the randomization of the last patient. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.Distant metastasis-free survival (DMFS) 2.Overall survival (OS) 3.•Severity of adverse events and SAEs on-study graded according to NCI CTCAE Version 5.0 •Changes from baseline and worst value on-study for clinical safety laboratory assessments, physical examinations, vital signs, ECGs, ECHO, dermatological examinations, ophthalmic examinations and ECOG performance status •Incidence of dose interruptions, dose modifications and discontinuation due to AEs and incidence of AEs requiring additional therapy 4. •The change in the HRQoL from baseline to the average of the scores during the treatment •The change in the HRQoL from baseline to week 48;Timepoint(s) of evaluation of this end point: 1. 6.9 years from first patient in 2.At the time of the DMFS analysis (6.9 years from first patient in) 3.At the time of the RFS analysis (4.7 years from first patient in) 4.At the time of the RFS analysis (4.7 years from first patient in) | — |
Countries
Australia, Austria, Belgium, Denmark, France, Germany, Italy, Netherlands, New Zealand, Norway, Poland, Spain, Sweden, Switzerland, United Kingdom
Contacts
Public ContactIsabelle Klauck
Pierre Fabre Médicament
Outcome results
None listed