Sample size
melanoma
MELANOMA
REFINE will enrol 160 patients into stage I for each cohort (80 patients randomised to each arm). This will provide 80% power at a 5% one-sided significance level to detect an absolute reduction of 20 percentage points in 9-month PFS. This number of patients would also be sufficient to demonstrate non-inferiority of the extended frequency arm, using a hazard ratio non-inferiority margin of 1.94 for the renal cohort (and e.g. 1.85 for the melanoma cohort) which should correspond to a 20-percentage points NI margin on the 9-month PFS difference scale. 9-month PFS rates are estimated to be 70% in the renal cohort [Following analysis of stage I data, assuming satisfactory outcomes in patients treated with the extended dosing interval, stage II will then test multiple experimental arms with the maximal interval being 3 times the SOC. The second stage intends to enrol up to an additional 200 patients per cohort dependent on stage I results. Under the same assumptions made for the stage 1 sample size calculations, this will provide around 80% power to demonstrate non-inferiority for the extended interval arm, relative to SOC using the same non-inferiority margins.