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 - COLUMBUS-AD

Pierre Fabre Médicament0 个研究点目标入组 815 人开始时间: 2022年4月5日最近更新: 2022年5月9日

适应症

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方
入组人数: 815

研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

暂无简介。

研究设计

研究类型: Interventional clinical trial of medicinal product

入排标准

性别: All

入选标准

•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 (pT3b-pT4bN0) 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;
•6.Available tumor sample for central determination of the BRAFV600E/K mutation. FFPE tumor tissue block or a minimum of 10 slides, optimally up to 20 slides.
•1.Before any related study activity, written informed consent must be given according to ICH/GCP, and national/local regulations;
•2.Melanoma confirmed centrally to be BRAF V600E/K mutation-positive;
•3.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 the randomization (Day 1);
•4.Randomization within 12 weeks from full surgical resection including sentinel lymph node biopsy (SLNB);
•5.Recovered from definitive surgery (e.g. complete wound healing, no uncontrolled wound infections or indwelling drains);
•6.ECOG performance status of 0 or 1;
•7.Adequate haematological function:
•i.Absolute neutrophil count (ANC) = 1.5 x 1000000000/L
•ii.Platelets = 100 x 1000000000/L
•iii.Hemoglobin = 9.0 g/dL
•8.Adequate renal function:
•Serum creatinine = 1.5 × ULN; or calculated creatinine clearance = 50 mL/min by Cockcroft Gault formula;
•9.Adequate electrolytes, defined as serum potassium and magnesium levels within institutional normal limits;
•10.Adequate hepatic function:
•i.Serum total bilirubin = 1.5 x ULN and < 2 mg/dL
•ii.Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) = 2.5 x ULN
•11.Adequate cardiac function:
•i.Left ventricular ejection fraction (LVEF) = 50% as determined by a multigated acquisition (MUGA) scan or echocardiogram
•ii.Mean triplicate QT interval corrected for heart rate according to Fridericia’s formula (QTcF) value = 480 msec and no history of QT syndrome
•12.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;
•13.Negative serum ß-HCG test (female patient of childbearing potential only) performed within 3 days prior to Day 1;
•14.Participants of childbearing / reproductive potential should use adequate birth control measures (see Appendix 4, section 10.4.2):
•Female participants are either postmenopausal for at least 1 year, surgically sterile for at least 6 weeks or must agree to take appropriate precautions to avoid pregnancy.
•Male participants must agree to take appropriate precautions to avoid fathering a child.
•Are the trial subjects under 18? no
•Number of subjects for this age range:
•F.1.2 Adults (18-64 years) yes
•F.1.2.1 Number of subjects for this age range 652
•F.1.3 Elderly (>=65 years) yes
•F.1.3.1 Number of subjects for this age range 163

排除标准

•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.
•1.Breast feeding women;
•2.Pregnancy;
•3.History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO.
•4.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 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;
•5.Previous or concurrent malignancy for the past 3 years. Except for non-melanoma skin cancer and any in situ cancer;
•6.Any condition with a life expectancy of less than 5 years;
•7.Participants with a prior cancer associated with RAS mutation;
•8.Previous treatment for melanoma beyond complete surgical resection (any prior systemic anticancer therapy; prior radiotherapy);
•9.Hypersensitivity to the study drugs or to any of the excipients;
•10.Participants with severe lactose intolerance;
•11.Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following:
•i.History of acute myocardial infarction, acute coronary syndromes (including unstable angina, coronary artery bypass graft, coronary angioplasty or stenting) = 6 months prior to randomization;
•ii.Congestive heart failure requiring treatment (New York Heart Association Grade = 2);
•iii.Uncontrolled hypertension defined as persistent systolic blood pressure = 150 mmHg or diastolic blood pressure = 100 mmHg despite optimal therapy;
•iv.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);
•12.Neuromuscular disorders that are associated with CK > ULN;
•13.Non-infectious pneumonitis and Interstitial Lung Disease;
•14.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;
•15.Participants with 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.
•Note: Participants receiving prophylactic antibiotics are exceptions and may participate.
•Note: Participants with a positive HBsAg (i.e., either acute or chronic active hepatitis) are excluded. Those with positive anti-HBcAb but negative HBsAg and anti-HBsAb profile may be eligible upon review and approval by the sponsor or designee.
•Note: Participants with positive HCV antibody but undetectable HCV viral load may be eligible upon review and approval by the sponsor or designee.
•Note: Participants with confirmed stable HIV disease may be eligible if they have viral load < 50 copies/mL and CD4 count > 200 cells/mm3, and on stable antiretroviral therapy for at least 6 months, provided that they meet all other study eligibility criteria. Testing for HIV is not mandated for study entry; however, testing must be per

研究者

发起方

Pierre Fabre Médicament

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