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

• Activity Number: 659 - Clinical Trial Research
• Type: Contributed
• Date/Time: Thursday, August 3, 2017 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Michelle DeVeaux* and Daniel Zelterman and Michael Kane
• Companies: Yale University and Yale University and Yale University
• Keywords: curtailed sampling ; discrete distribution ; expected sample size ; lung cancer ; minimax design ; power

Abstract

We propose a two-stage design for a clinical trial with an early stopping rule for safety. This design employs different criteria to assess early stopping and efficacy. The early stopping rule is based on a criterion that can be determined more quickly than 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 criteria. We are developing an R package and Shiny web application that allow for easy planning of this design in terms of statistical significance, power, and expected sample size under curtailed and traditional sampling. We also examine the expected duration of the design compared to a traditional two-stage design. This method is illustrated with a Phase II design comparing patients treated for lung cancer with a novel drug combination to 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.