Adaptive Two-Stage Designs for Heterogeneous Patient Populations in Phase II Cancer Trials

• Activity Number: 284
• Type: Contributed
• Date/Time: Tuesday, July 31, 2007 : 10:30 AM to 12:20 PM
• Sponsor: Biometrics Section
• Author(s): Karen Messer*+ and Michael Donohue
• Companies: University of California, San Diego and University of California, San Diego
• Keywords: Phase II trials ; group sequential design ; two stage design ; adaptive design

Abstract

In a Phase II cancer trial there may be several patient groups. For example, in a Leukemia trial patients in 1st relapse may have 30% probability of response under standard treatment while patients in 2nd + relapse may have only 10% probability of response. In many cancer trials the experimental agent is expected to induce severe toxicity. Such trials are usually designed with a stopping rule which checks for initial evidence of efficacy after a first stage enrollment target is met. If there is insufficient evidence, the trial stops early for futility. We discuss the standard two-stage designs in this situation, and describe their operating characteristics under heterogeneous patient enrollment. Simple, approximately optimal designs which account for heterogeneity are presented. We recommend a practical adaptive design strategy which we have implemented at Moores UCSD Cancer Center.