Circulating tumour DNA guidEd Therapy for stage IIB/C BRAF mutant positive mElanoma after surgiCal resecTION (DETECTION)

DETECTION is a Phase III open label, multicentre trial that aims to use the detection of BRAF/NRAS/TERT promoter mutations in circulating tumour DNA (ctDNA) to detect early relapse before it is clinically apparent. Patients with stage IIB/C melanoma (n=1050) will have longitudinal ctDNA sampling at baseline and at clinic visits every 3 months in years 1-3, every 6 months in years 4-5, and annually thereafter, until evidence of clinical/radiological progression or close of study. Patients with ctDNA detected will be randomised immediately after the result has been quality assured, 1:1 to one of two arms.
In arm A, patients and clinicians will remain blinded to the ctDNA result. Patients will continue to be monitored with regular clinical examination and imaging and will only be treated if they develop clinical and/or radiological recurrence. Patients randomised to Arm B will be unblinded to the positive ctDNA result and treated early with immunotherapy. This study will test whether: 1) ctDNA detects recurrence earlier than clinical review and imaging and 2) whether earlier treatment of recurrent disease based on ctDNA positivity results in better overall survival (OS). The study has an early feasibility assessment and an interim analysis for relapse free survival ahead of the primary analysis of OS. This investigator initiated study has received funding from Cancer Research United Kingdom (UK) to undertake the study in UK. We seek MRFF funding to conduct this important study in Australia. If our hypothesis is confirmed, DETECTION will show that molecular monitoring and early treatment based on ctDNA improves OS and should be implemented as standard of care in stage IIB/C melanoma. It will also provide the framework to undertake similar risk stratified trials for patients with stage III melanoma. DETECTION will provide valuable clinical samples for translational research into other predictors of patients at high risk of relapse and early detection of recurrence.