Randomized phase II/III confirmatory treatment selection design with a change of survival end points: Statistical design of Radiation Therapy Oncology Group 1216

To confirm the treatment effects of concurrent cetuximab plus docetaxel observed in Radiation Therapy Oncology Group (RTOG) 0234 and single out the effect of cetuximab, we designed RTOG 1216, a randomized phase II/III study, which uses an intermediate end point to select the best regimen for definitive testing of survival benefit.

In phase II, the best regimen should demonstrate statistically significant efficacy against the control with predefined advantage over the competing arm regarding disease-free survival (DFS). We evaluate operating characteristics of the randomized II/III group sequential design through simulations and numerical integrations under the null and various alternative hypotheses.

Results show the randomized II/III design yields substantial savings on sample size and time with well-controlled type I and type II error rates.

Overall, the proposed randomized II/III design has desirable properties that offer cost effectiveness, operational efficiency, and, most importantly, scientific innovation that can be considered for similar clinical research settings.