in transit metastases melanoma
Conditions
Interventions
Patients diagnosed with in-transit melanoma metastases will receive
encorafenib/binimetinib in the neo-adjuvant setting for 8 weeks according to
the schedule depicted below. Additionally, patients w
Sponsors
Academisch Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Age over 18 years old 2. World Health Organization (WHO) Performance Status 0 or I 3. Primary cutaneous melanoma or unknown primary melanoma with pathologically confirmed in-transit metastatic melanoma 4. Histologically confirmed presence of BRAFV600E/K mutation in primary tumor tissue 5. Patients must have undergone complete disease staging including: PET-CT scan and MRI scan 6. Patients must be medically fit to undergo surgery 7. Patients must be able to take oral medication 8 No prior anticancer systemic treatment (including chemotherapy, immunotherapy, oncolytic viral therapy, other systemic therapies) 9. No prior radiotherapy to site of interest (surgical therapy is allowed; in order to obtain pathological information of the melanoma) 10. 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 = 50 mL/min by Cockcroft-Gault formula; or estimated glomerular filtration rate > 50 mL/min/1.73m2. 11. Absence of additional severe and/or uncontrolled concurrent disease 12. Patients known to be human immunodeficiency virus (HIV) positive are eligible if they have undetectable HIV viral load and stable and adequate CD4 counts (>= 500 mm^3) on screening labs provided they meet all other protocol criteria for participation and that there are no high-risk drug interactions
Exclusion criteria
Exclusion criteria: 1. Presence of regional lymph node metastases 2. Presence of distant metastases 3. Current treatment with antiretroviral drugs, herbal remedies and drugs that are strong inhibitors or inducers of CYP3A and CYP2C8 4. Patients with active bacterial infections with systemic manifestations (malaise, fever, leukocytosis) are not eligible until completion of appropriate therapy 5. 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 6. 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. 7. History of central serous retinopathy or retinal vein occlusion 8. Active intestinal disease interfering with oral drug absorption 9. Patients who are unable to be temporally removed from chronic anti-coagulation therapy 10. Other malignancy within 2 years prior to entry into the study, except for treated non-melanoma skin cancer and in situ cervical carcinoma 11. 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 12. Patient must not have any known history of acute or chronic pancreatitis 13. 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 14. Pregnancy or nursing
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary study endpoint is to determine efficacy of neo-adjuvant BRAF/MEK inhibition with encorafenib/binimetinib in patients with histologically confirmed in-transit melanoma metastases, measured as partial-, complete- or no response. In the biopsy at week 0 the viability will be judged and will be graded according to the amount of tumor necrosis: >50% tumor necrosis with 50% viable tumor cells and 100% necrosis without viable tumor cells. Partial response is defined as a decrease of at least 50% of the viable tumor cells, compared to the baseline measurement, week 0, and complete response as 100% decrease of tumor cells, whereas no response is defined as more than 50% of viable tumor cells present. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints/parameters are: toxicity according to CTCAE v 5.0, recurrence free survival (RFS); defined as the time from inclusion into the study to recurrence of disease (local and/or distant), distant metastasis free survival (DMS) defined as the moment from inclusion into the study to recurrence event (distant) and overall survival (OS); defined as moment of inclusion into the study up to the last moment alive. | — |
Countries
Netherlands
Outcome results
None listed