The Calibration of the TITE-CRM Design for Phase I Cancer Trials with Fast Patient Accrual

• Activity Number: 322
• Type: Contributed
• Date/Time: Tuesday, August 4, 2009 : 10:30 AM to 12:20 PM
• Sponsor: Biometrics Section
• Author(s): Mei-Yin Polley*+
• Companies: University of California, San Francisco
• Keywords: phase I clinical trials ; time-to-event continual reassessment method (TITE-CRM) ; dose-limiting toxicity (DLT) ; 3+3 design ; late toxicity

Abstract

The goal of phase I cancer trials is to determine the highest dose of a treatment regimen with an acceptable toxicity rate. Traditional designs for phase I trials, such as the CRM and 3+3 design, require each patient or a cohort of patients to be fully evaluated for the DLT before new patients can be enrolled. As such, the trial duration may be prohibitively long. The TITE-CRM by Cheung and Chappell addresses this limitation by allowing staggered patient accrual. However, when patient accrual is fast (e.g. multi-center or consortium trials), the TITE-CRM may result in overly aggressive dose escalation especially when late toxicities are expected. We discuss practical considerations of TITE-CRM and propose modifications necessary in this setting. A neuro-oncology trial is used to demonstrate the design calibrations. Simulations are used to compare the TITE-CRM design and the 3+3 design.