A Phase II--III Design with Biomarker-Guided Subpopulation Selection and Its Application to a Case Study of NCIC CTG Trial

• Activity Number: 125
• Type: Contributed
• Date/Time: Monday, August 4, 2014 : 8:30 AM to 10:20 AM
• Sponsor: SSC
• Author(s): Keyue Ding*+
• Companies: Queen's University
• Keywords: Biomarker ; Phase II/III design ; Clinical trial ; Targeted therapy ; Multiple test ; sensitive subgroup

Abstract

Targeted therapies aimed at the molecular pathways involved in oncogenesis have led to development of highly specific cancer treatments with greater efficacy and lower toxicity than conventional cytotoxic agents. With the knowledge of the study drug's mechanism of action, there are some rationales that the drug may be more effective in patients with certain biomarker defined subgroup, but its effect in the whole population is also highly interested. Clinical Trial design with multiple test populations: Overall population, Pre-specified biomarker defined subgroup would be a suitable choice for such study. In this paper, we proposed a phase II/III design with biomarker guided subpopulation selection at the end of phase II analysis. Decision rule of the final analysis is proposed taking multiple tests and correlation of test statistics between the whole population and the subpopulation into account. Simulation studies showed the design is with very satisfactory statistical operational characteristics. Its application to a NCIC CTG trial demonstrated an excellent fit for the case with a biomarker defined sensitive subgroup.