Adaptive Design of Oncology Trials Using Change in Tumor Size at Interim Analysis

• Activity Number: 17
• Type: Topic Contributed
• Date/Time: Sunday, August 4, 2013 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Bin Zhang*+ and Jing Wang
• Companies: Millennium Pharmaceuticals, Inc. and Boston University and Boston University School of Public Health
• Keywords: adaptive design ; oncology clinical trials ; tumor size change

Abstract

Progression Free Survival (PFS) and Overall Response Rate (ORR) have been commonly used endpoints in oncology clinical trials, yet both are easily subject to measurement errors and misclassication due to the arbitrary nature of the cutos that denes PFS and ORR. Neither necessarily translate into Overall Survival (OS) benet. We propose a continuous measure, the tumor size change at landmark time that are subject to measurement error to a lesser degree than that of PFS and ORR, as a substitue for OS at interim analysis to make clinical trials decisions, including increasing sample size if necessary. Using established model that relating OS to tumor size chagne at landmark time, we show the equivalencies of designing clincial trials using tumor size change at landmark time and OS benet. We apply this method in a specic design to demonstration the advantages of using tumor size change at interim analysis that enables desicions on sample size adaption at much earlier time than using PFS or OS at interim analysis.