Clinical Trial Designs for Biomarker Research in Oncology

• Activity Number: 407
• Type: Topic Contributed
• Date/Time: Tuesday, August 6, 2013 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Sumithra Mandrekar*+
• Companies: Mayo Clinic
• Keywords: Biomarkers ; Clinical trial design ; enrichment design ; all-comers design ; phase II designs

Abstract

Several prospective designs for biomarker-directed therapy have been proposed, differing primarily in the study population, or randomization scheme, or both. The design choice is driven by scientific rationale, marker prevalence, strength of preliminary evidence, assay reliability and validity, and turn-around times for marker assessment. The enrichment design is most appropriate when compelling preliminary evidence suggests treatment benefit in only certain marker-defined subgroups, the all-comers design is useful when preliminary evidence regarding treatment effects in marker subgroups is unclear, and adaptive designs have the most potential in a phase II setting where multiple treatment options and/or multiple marker-defined subgroups are investigated within the same trial. In the setting of initial marker validation, i.e., phase II setting, we recently proposed a 2-stage design that has the option for direct assignment (i.e., stop randomization and assign all patients to the experimental arm in Stage 2) based on interim analysis (IA) results. I will use examples of real clinical trials, when available, to illustrate these design concepts.