Implementation of Patient Enrichment Design in a Phase II Oncology Trial

• Activity Number: 606
• Type: Topic Contributed
• Date/Time: Thursday, August 2, 2012 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): James Song*+
• Companies: Roche
• Keywords: power calculation ; enrichment design ; interim analysis

Abstract

Adaptive design (AD) is a clinical trial design that allows adaptations of a trial design after its initiation without undermining the validity and integrity of the trial. FDA encourages sponsors to use less well-understood AD in exploratory studies that have less impact on regulatory approval decisions while taking advantage of the benefit that AD offers.

Application of AD in early development is discussed through a two-stage design with an interim futility analysis in a randomized phase 2 trial for patients with different levels of biomarker positivity. The primary objectives are to demonstrate treatment effect in all biomarker positive patients (H01+) and in a subset of biomarker highly expressed patients (H02+). A futility assessment in H01+ is planned at the end of stage 1 to evaluate the efficacy in all positive patients in order to limit the risk of exposing more patients with low expression to study drug. The power consideration and interim decision rule will be discussed as well as some of the concerns that are raised. The goal is to show that a carefully designed AD can offer efficiency, speed and flexibility without compromising the integrity of the trial.