A Two-Stage, Phase II Clinical Trial Design with Nested Criteria for Early Stopping and Efficacy

We propose a two-stage design for a clinical trial with an early stopping rule for safety. We use different criteria to assess early stopping and efficacy. The early stopping rule is based on a criteria that can be determined more quickly than that of efficacy. These separate criteria are also nested in the sense that efficacy is a special case of, but not identical to, the early stopping criteria. The design readily allows for planning in terms of statistical significance, power, and expected sample size necessary to assess an early stopping rule. This method is illustrated with a Phase II design comparing patients treated for lung cancer with a novel drug combination to those treated using historical control. In this example, the early stopping rule is based on the numbers of patients who exhibit progression-free survival (PFS) at 2 months post treatment follow-up and efficacy is judged by the number of patients who have PFS at 6 months.