Escalation with Overdose Control Using Normalized Equivalent Toxicity Score and Patient's Characteristics to Define Personalized Maximum Tolerated Dose in Phase I Clinical Trial

• Activity Number: 70
• Type: Contributed
• Date/Time: Sunday, July 31, 2011 : 4:00 PM to 5:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Zhengjia Chen*+ and Mourad Tighiouart and Yuan Liu and Zhibo Wang and Taofeek K. Owonikoko and Jeanne Kowalski
• Companies: Emory University and Emory University and Emory University and Georgia State University and Emory University and Emory University
• Keywords: Escalation With Overdose Control (EWOC) ; Cancer Phase I Clinical Trials ; Normalized Equivalence Toxicity Score (NETS) ; Personalized Maximum Tolerated Dose ; Adaptive Bayesian Design ; Escalation with overdose control using normalized equivalent toxicity score (EWOC-NETS)

Abstract

An individualized approach to define personalized maximum tolerated dose (MTD) of novel therapeutic agent is a critical step advancing towards the goal of personalized cancer therapy. We have extended escalation with overdose control (EWOC) to account for all toxicities of patients by using a normalized equivalent toxicity score (NETS) instead of probability of dose limiting toxicity (DLT). The design is termed EWOC-NETS. In the presence of a binary indicator of DLT, Babb and Rogatko (2001) and Tighiouart and Rogatko (2010) extended EWOC to account for patients' baseline covariates in order to estimate patients' specific phase II dose. We plan to extend EWOC-NETS by adjusting for baseline covariates thought to be susceptible to the NETS. Design operating characteristics will be evaluated with extensive simulations by comparing models with respect to the accuracy and efficiency of the est