Circulating Tumour DNA guidEd Therapy for Stage IIB/C mElanoma After surgiCal resecTION

Inclusion Criteria

• •1. Signed written informed consent.
• •2. Patients must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests and other requirements of the study.
• •3. Histological confirmation of cutaneous melanoma
• •4. ≥ 18 years.
• •5. Stage IIB or IIC melanoma (sentinel lymph node (SNLB) staged) according to AJCC version 8 (4).
• •6. Complete resection (including SNLB) must have been performed within 12 weeks prior to registration.
• •7. Disease-free status documented both clinically and radiologically within 4 weeks prior to registration.
• •8. Mutation confirmed in at least one of the following BRAF (p.V600E/p.V600K/p.V600R) /NRAS (p.Q61R/p.Q61K, p.Q61L/p.G12D), which can be tracked in ctDNA with exact point mutation known.
• •9. ECOG performance status 0/1.
• •10. Adequate organ function and screening laboratory values must meet the following criteria: WBC ≥ 2.0x109/L, Absolute neutrophil count (ANC) ≥1.5x109/L, Platelets ≥100 x109/L, Haemoglobin ≥90 g/L, Creatinine ≤1.5x ULN or creatinine clearance \>30mL/minute using Cockcroft-Gault, AST ≤ 1.5 x ULN, ALT ≤ 1.5 x ULN, Bilirubin ≤1.5 x ULN unless the patient has familial hyperbilirubinaemia.
• •11. LDH ≤1.5x ULN as per local institution parameters.
• •12. Patients who are pregnant or breastfeeding will be eligible to join the trial. However, if they are allocated to Arm B, women of childbearing potential (WOCBP) must agree to have a serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) and must be withdrawn if pregnant or breastfeeding. WOCBP and males who are sexually active with WOCBP must also agree to follow instructions for method(s) of contraception for the duration of treatment plus 5 months for WOCBP or plus 7 months for males who are sexually active with WOCBP (if randomised to Arm B or while receiving any systemic treatment and to follow local guidance if given on Arm A). See Appendix A for further information.