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

Phase 3

Completed

• Conditions: Melanoma; skin cancer; 10040900

• Registration Number: NL-OMON52293
• Lead Sponsor: Pierre Fabre

Brief Summary

Trial ended prematurely

Detailed Description

Not available

Study Timeline

• Study Completion: 2024-05-30
• Last Update Posted: 9 September 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 31

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 (pT3bpT4bN0)
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.

Screening
1.Before any related study activity, written informed consent must be
given according to ICH/GCP, and national/local regulations;
2.Presence of BRAF V600E/K mutation in tumor tissue as determined by
a local assay any time prior to screening (if done routinely in clinical
practice) and/or the central laboratory
i.If the participant is screened based on local assay result, the BRAF
V600E/K mutation status must be confirmed by the central laboratory
prior to randomization.
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 β-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.

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.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 antire

Study & Design

• Study Type: Interventional
• Study Design: Not specified