Sequential Design of Phase II--III Cancer Trials

• Activity Number: 569
• Type: Topic Contributed
• Date/Time: Wednesday, August 4, 2010 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Tze Leung Lai and Philip Lavori and Mei-Chiung Shih*+
• Companies: Stanford University and Stanford University and Stanford University
• Keywords: Cancer clinical trials ; Group sequential designs ; Phase II-III designs ; Survival analysis

Abstract

Whereas traditional Phase II cancer trials are single-armed, with tumor response as endpoint, and Phase III trials are randomized and long-term, with interim analyses and failure time as endpoint, we propose a new approach that seamlessly expands a randomized Phase II study of response rate into a randomized Phase III study of failure time. This approach is built on recent advances in adaptive and group sequential designs and joint modeling of response rate and failure time. The joint modeling is reflected in the set of primary and secondary objectives of the trial and their analysis; the sequential design allows the trial to adapt to increase in information on response and survival patterns during the course of the trial, and to stop early either for a definitive conclusion on efficacy or for need to redesign the trial or even abandon the biological hypotheses underlying the treatment.