Two-stage phase II survival trial design

Abstract

Recently, molecularly targeted agents and immunotherapy have been advanced for the treatment of relapse or refractory cancer patients, where disease progression-free survival or event-free survival is often a primary endpoint for the trial design. However, methods to evaluate two-stage single-arm phase II trials with a time-to-event endpoint are currently processed under an exponential distribution, which limits application of real trial designs. In this paper, we developed an optimal two-stage design, which is applied to the four commonly used parametric survival distributions. The proposed method has advantages compared with existing methods in that the choice of underlying survival model is more flexible and the power of the study is more adequately addressed. Therefore, the proposed two-stage design can be routinely used for single-arm phase II trial designs with a time-to-event endpoint as a complement to the commonly used Simon's two-stage design for the binary outcome.

Keywords: one-sample log-rank test; phase II trial; sample size; time-to-event; two-stage design.