Exploring Futility and Enrichment in the Context of a Multi-Arm Phase II Oncology Study

• Activity Number: 172
• Type: Contributed
• Date/Time: Monday, August 4, 2014 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Grace Zhang*+ and Liz Krachey and Anthony M. D'Amelio and Vlad Dragalin
• Companies: GlaxoSmithKline and GlaxoSmithKline and GlaxoSmithKline and Aptiv Solutions
• Keywords: enrichment ; futility ; adaptive design ; Oncology

Abstract

This design is considered when there are two drugs (Drug A and Drug B) that target 2 receptors that are implicated in one type of cancer. This study will examine each of these drugs in combination with the standard of care (SOC) for this cancer and compare them with the SOC in biomarker negative patients. An adaptive design is proposed with an interim analysis when 50% of patients have their response. The purpose of the interim analysis is to select one of the combination treatment arms and to determine the sample size for the second stage to achieve the 80% conditional power. The treatment selection is implemented through a beta-spending function. In case the Drug B is selected for the second stage, the enrollment of biomarker positive subjects may be initiated. In order to maintain the family wise error rate under one-sided 5%, the inverse normal p-value combination method and closed testing procedure is used in the final analysis.