Adaptive seamless design for an efficacy trial of replication-competent adenovirus-mediated suicide gene therapy and radiation in newly-diagnosed XXXX (ReCAP Trial).

@entity1 @entity137 @entity263 @entity18504 @entity489
PURPOSE: Cumulative evidence has suggested investigation of the efficacy of Replication-Competent Adenovirus-mediated Suicide Gene Therapy in newly-diagnosed @entity263 (ReCAP). There is a challenge in designing an efficacy trial for newly-diagnosed @entity263 given its long natural history. The regulatory agency recommended a Phase II trial for safety before conducting the efficacy trial. EXPERIMENTAL DESIGN: The ReCAP trial is an adaptive seamless, multi-site open-label, randomized Phase II/III trial. Two hundred eighty @entity1 will be randomized to receive either replication-competent adenovirus-mediated suicide gene therapy followed by radiation ( @entity18504 ) or radiation alone ( @entity489 ). Phase II trial component will include the first 21 @entity1 in @entity18504 with complete @entity137 through day 90 for safety evaluation. The primary efficacy endpoint is the time free from biochemical and/or clinical failure (FFF). The secondary efficacy endpoints are 2-year prostate biopsies and overall survival. Unequal spaced interim looks are proposed with the adaptive sample-size re-estimation. RESULTS: This trial has been approved by the FDA for the study therapy investigation and is currently recruiting @entity1 . CONCLUSIONS: Challenges remain in designing newly-diagnosed @entity263 trials. Adaptive seamless design is time-saving and a cost-effective design in the development of novel medical therapies, but requires a specified statistical plan in the decision process involved.
