Treatment Prioritization in Phase I Umbrella Protocol for Targeted Cancer Therapies

• Activity Number: 507
• Type: Invited
• Date/Time: Wednesday, August 12, 2015 : 10:30 AM to 12:20 PM
• Sponsor: ENAR
• Author(s): Yimei Li* and Ming Wang and Ken Cheung
• Companies: University of Pennsylvania and Penn State and Columbia University
• Keywords: cancer clinical trial ; targeted therapy ; continuous reassessment method ; adaptive randomization

Abstract

A phase I trial typically aims to evaluate the safety of a therapy and identify the MTD. With the development of target therapies, the efficacy of a therapy depends on the biomarkers of a patient and oftentimes several candidate therapies exist for a given cancer disease. There are increasing interests in conducting a platform trial that evaluates multiple therapies for various biomarkers associated with the disease. Because a patient with a given biomarker could be eligible for multiple drugs, prioritization of these drugs becomes an important aspect and in this project we propose utilizing adaptive randomization (AR). The AR ratio is updated based on the observed efficacy data, using a hierarchical Bayesian model that incorporates information across different dose levels. We use the established CRM method to determine MTDs of the drugs. We demonstrate that our approach will correctly prioritize the candidate drugs, identifying the drug that works better for patients with a particular biomarker. Moreover compared to conducting separate parallel CRM trials, our approach will provide more robust MTD estimate for the drug that is effective for patients with a certain biomarker.