A Dose-Escalation Design for Combination Cancer Therapies

• Activity Number: 407
• Type: Topic Contributed
• Date/Time: Tuesday, August 6, 2013 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Jenny Zhang*+
• Companies: Gilead Sciences
• Keywords: Dose escalation ; combination therapies ; oncology ; clinical trials ; Phase I/II ; intra-patient escalation

Abstract

Current dose escalation methods in Phase I/II clinical trials to evaluate new anticancer agents include both rule-based and model-based strategies. Toxicity is the traditional primary endpoint for such trials. Performance evaluation of different dose escalation methods is primarily based on minimizing the number of patients exposed to sub- therapeutic doses while protecting safety and maintaining accrual. Combination therapies, which are becoming increasingly prevalent in cancer drug development, are an added complexity to dose escalation trials. This paper describes a dose escalation design for a new anticancer drug combination, which involves intra-patient escalations and modifications of the starting dose level for subsequently enrolled patients. The performance characteristics of the proposed design will be evaluated via a simulation study.