(Neo)Adjuvant BRAF/MEK Inhibition in pN1c Melanoma

Launched by LEIDEN UNIVERSITY MEDICAL CENTER · Mar 2, 2023

Keywords

ClinConnect Summary

This clinical trial is studying a treatment approach for patients with a specific type of melanoma known as in-transit melanoma, which has spread to nearby tissues but not to lymph nodes or distant organs. The trial involves giving patients two medications, encorafenib and binimetinib, before surgery to see if this helps improve their outcomes. After surgery, patients will continue to receive these medications to help prevent the melanoma from returning.

To be eligible for this trial, participants need to be at least 18 years old, have confirmed in-transit melanoma, and must be in good health to undergo surgery. They should not have received prior cancer treatments, and certain health conditions may disqualify them. Patients participating in the trial can expect to take oral medications and undergo regular monitoring, including scans, to track their progress. It's important to know that the trial is currently recruiting, and all genders are welcome to participate.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Age over 18 years old
• • World Health Organization (WHO) Performance Status 0 or I
• • Primary cutaneous melanoma or unknown primary melanoma with pathologically confirmed in-transit metastatic melanoma
• • Patients must have undergone complete disease staging including: PET-CT scan and MRI scan
• • Patients must be medically fit to undergo surgery
• • Patients must be able to take oral medication
• • No prior anticancer systemic treatment (including chemotherapy, immunotherapy, oncolytic viral therapy, other systemic therapies)
• • No prior radiotherapy to site of interest (surgical therapy is allowed; in order to obtain pathological information of the melanoma)
• • Screening laboratory values must meet the following criteria: WBC ≥ 2.0x109/L, Neutrophils ≥ 1.0x109/L, Platelets ≥ 100 x109/L, Hemoglobin ≥ 6.5 mmol/L, AST ≤ 2.5 x ULN, ALT ≤ 2.5 x ULN, Total bilirubin ≤ 1.5 X ULN, INR and PTT in normal range, LDH \< 2xULN. Serum creatinine ≤ 1.5 × ULN; or calculated creatinine clearance ≥ 50 mL/min by Cockcroft-Gault formula; or estimated glomerular filtration rate \> 50 mL/min/1.73m2.
• • Absence of additional severe and/or uncontrolled concurrent disease
• Exclusion Criteria:
• • Presence of regional lymph node metastases
• • Presence of distant metastases
• • Current treatment with antiretroviral drugs, herbal remedies and drugs that are strong inhibitors or inducers of CYP3A and CYP2C8
• • Patients with active bacterial infections with systemic manifestations (malaise, fever, leukocytosis) are not eligible until completion of appropriate therapy
• • Underlying medical conditions that, in the Investigator's opinion, will make the administration of study treatment hazardous or obscure the interpretation of toxicity determination or adverse events
• • History of congestive heart failure, active cardiac conditions, including unstable coronary syndromes (unstable or severe angina, recent myocardial infarction), significant arrhythmias and severe valvular disease must be evaluated for risks of undergoing general anesthesia. Furthermore, enlarged QTc interval, uncontrolled hypertension, poor left ventricular function (\< 50%, as determined by MUGA scan) and recent thromboembolic or cerebral event.
• • History of central serous retinopathy or retinal vein occlusion
• • Active intestinal disease interfering with oral drug absorption
• • Patients who are unable to be temporally removed from chronic anti-coagulation therapy for operation
• • (Neo)Adjuvant BRAF/MEKi for pN1c melanoma, version 5, 31 October 2021
• • Other malignancy within 2 years prior to entry into the study, except for treated non-melanoma skin cancer and in situ cervical carcinoma
• • Patient must not have active hepatitis B, and/or active hepatitis C infection given concerns for drug interactions or increased toxicities. Testing is not required
• • Patient must not have any known history of acute or chronic pancreatitis
• • Patient must not have any concurrent neuromuscular disorder that is associated with elevated creatine kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy
• • Pregnancy or nursing