Phase II Trial Designs to Evaluate Clinical Efficacy of Personalized Drug Selection Based on an In Vitro Sensitivity Screen

• Activity Number: 232
• Type: Contributed
• Date/Time: Monday, August 1, 2011 : 2:00 PM to 3:50 PM
• Sponsor: Biometrics Section
• Author(s): Motomi Mori*+ and Yiyi Chen and Byung S. Park and Jeffrey W. Tyner and Marc M. Loriaux and Tibor Kovacsovics and Brian J. Druker
• Companies: Oregon Health & Science University and Oregon Health & Science University and Oregon Health & Science University and Oregon Health & Science University and Oregon Health & Science University and Oregon Health & Science University and Oregon Health & Science University
• Keywords: clinical trials ; cancer ; phase II trials ; personalized medicine

Abstract

We have recently developed a novel in vitro screening technique to evaluate sensitivity of primary cells from leukemia patients against a panel of small-molecule kinase inhibitors. To evaluate the clinical utility of drug selection based on in vitro drug sensitivity, we propose two different randomized phase II trial designs, both involving multiple kinase inhibitors: 1) a single randomization design in which patients are randomized to receive a drug predictive to be effective or one of the other drugs not predictive to be effective, with a higher probability of being assigned to a predicted drug, and 2) a double randomization design in which patients are first randomized to an assay-based drug assignment or randomly selected drug assignment, and those in the randomly selected drug assignment are further randomized to receive one of the drugs under study. We will evaluate operating characteristics of two designs and performance of the proposed frequentist and Bayesian test statistics through simulations. We will conclude our presentation by discussing statistical issues and challenges in testing genome/biomarker-guided strategy or more generally "personalized medicine".