Biomarker-Based Dose-Finding Designs for Single- or Multiple-Agent Phase I Trials

• Activity Number: 72
• Type: Contributed
• Date/Time: Sunday, August 3, 2014 : 4:00 PM to 5:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Yuan Xue*+ and Mark Conaway and Feifang Hu
• Companies: University of Virginia and University of Virginia and George Washington University
• Keywords: Biomarker ; Continual Reassessment Method ; Partial ordering ; Dose-finding studies ; Maximum Tolerated Dose

Abstract

The primary goal of a Phase I clinical trial is to estimate the maximum tolerated dose (MTD). We address two practical considerations: heterogeneous toxicity response and a partial ordering for the probability of toxicity for available treatments. We propose a new design which chooses a distinct MTD for individual patient by use of toxicity biomarker information, thus contributing to proper and better treatment for individual patient. We extend the biomarker-based design to include multiple-agent trials. The operating characteristics of the proposed designs are investigated through extensive simulation studies. A discuss of the theoretical properties is provided. We close with some conclusions drawn from the proposed biomarker-based designs, as well as some topics for future research.