A two-stage phase II clinical trial design with nested criteria for early stopping and efficacy.

We propose a two-stage design for a single arm clinical trial with an early stopping rule for futility. This design employs different endpoints to assess early stopping and efficacy. The early stopping rule is based on a criteria determined more quickly than that for efficacy. These separate criteria are also nested in the sense that efficacy is a special case of, but usually not identical to, the early stopping endpoint. The design readily allows for planning in terms of statistical significance, power, expected sample size, and expected duration. This method is illustrated with a phase II design comparing rates of disease progression in elderly patients treated for lung cancer to rates found using a historical control. In this example, the early stopping rule is based on the number of patients who exhibit progression-free survival (PFS) at 2 months post treatment follow-up. Efficacy is judged by the number of patients who have PFS at 6 months. We demonstrate our design has expected sample size and power comparable with the Simon two-stage design but exhibits shorter expected duration under a range of useful parameter values.