Novel Phase I Design for Oncology Research

• Activity Number: 18
• Type: Topic Contributed
• Date/Time: Sunday, August 1, 2010 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Linda Sun*+ and Keaven M. Anderson and Lisa Lupinacci and Yevgen Tymofyeyev
• Companies: Merck & Co., Inc. and Merck Research Laboratories and Merck & Co., Inc. and Merck & Co., Inc.
• Keywords: Phase I oncology ; Bayesian ; Adaptive

Abstract

The primary objective of Phase I oncology studies is to identify a dose with an acceptable toxicity rate to move into Phase II efficacy studies. Various Phase I oncology designs have been proposed in the past, from the simplest 3+3 design to the more complex continuous reassessment method (CRM). In this talk, we will introduce an easy-to-implement Bayesian adaptive design which makes dose escalation or de-escalation based on the posterior probability of the toxicity rate at the dose level currently being tested. Simulation results show that this novel design out-performs the 3+3 design with higher probability of choosing the dose with the targeted toxicity rate. It slightly under-performs the CRM design. However, this design can show the dose escalation rules in a simple table before the study starts. This feature is very appealing to physician, regulatory reviewers, and IRBs.