Dose-Finding Methods Based on Cure Model Approach in Phase I Cancer Clinical Trials

• Activity Number: 45
• Type: Contributed
• Date/Time: Sunday, August 9, 2015 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Menghui Chen* and Yong Lin and Weichung Joe Shih
• Companies: Merck and Rutgers University and Rutgers University
• Keywords: Dose Finding ; Phase I Cancer Clinical Trial ; Cure Model ; CRM ; EWOC ; Hybrid design

Abstract

The main goal of a phase I cancer clinical trial is to identify the MTD of a new drug having acceptable dose-limiting toxicity (DLT). Two main model-based designs are CRM and EWOC. Most of the designs are based on the binary toxic outcome. Information is lost by categorizing time-to-DLT to a binary variable and might lead to a poor estimate of MTD. Some methods have been proposed to incorporate the time-to-DLT using a weight function, such as TITE-CRM and TITE-EWOC. A better approach would be to model the time-to-DLT data directly for patients who will experience the DLT and to separate these patients from those who will never experience the DLT given a specific dose. This approach can be based on the well-studied cure model. We will develop a Bayesian design framework based on cure model approach to incorporate the time-to-DLT and will extend the current model-based designs such as CRM, EWOC or the hybrid design. We will call it CATE design for Cure rate model Approach for Time-to-DLT Event. Extensive simulation studies had been conducted, and the results shows that CATE designs outperform the existing designs for phase I cancer clinical trials.