A Novel Phase II Design to Minimize Trial Duration and Improve the Success Rate of Follow-Up Phase III Trial

• Activity Number: 562
• Type: Topic Contributed
• Date/Time: Wednesday, August 1, 2012 : 2:00 PM to 3:50 PM
• Sponsor: Biometrics Section
• Author(s): Ye Cui*+ and Taofeek K Owonikoko and Zhibo Wang and Sungjin Kim and Dong M Shin and Fadlo R Khuri and Jeanne Kowalski and Zhengjia Chen
• Companies: Georgia State University and Emory University and Winship Cancer Institute and Winship Cancer Institute and Emory University and Emory University and Biostatistics and Bioinformatics Shared Resource at Winship Cancer Institute and Biostatistics and Bioinformatics Shared Resource at Winship Cancer Institute
• Keywords: Double screening ; Phase II design ; Success rate of Phase III trials ; Percent of Tumor Size Change ; Progression free survival ; Cost and length of trial

Abstract

A Phase II trial is an expeditious and low cost trial with the primary goal of screening potentially effective agents prior to confirmatory Phase III trial. The success rate of Phase III oncology trials remains very low despite the success demonstrated in the preceding Phase II trials. This discordance is mainly due to the different endpoints used in Phase II (disease response) and III (survival) trials. While a robust disease response is expected to translate into survival improvement, this is NOT guaranteed. Moreover, disease response can be determined quickly whereas survival estimation requires a long period of follow up. We propose a novel 2-stage screening design for phase II trials whereby percent of tumor size change endpoint is used as an initial screening to select potentially effective agents within a short time interval followed by a second screening stage where progression free survival is estimated to confirm the efficacy of agents. This design can improve trial efficiency and reduce cost by early stopping the evaluation of an ineffective agent based on low percent of tumor size change. The second survival endpoint screening will substantially increase the success rate of follow-up Phase III trial by using the similar outcomes. We conducted simulation studies to investigate the underlying statistical considerations to optimize the significant levels of the two screening stages in the design.