Regulatory Aspects of Phase I Designs in Oncology Trials
*Somesh Chattopadhyay, FDA  Rajeshwari Sridhara, FDA  Shenghui Tang, FDA  Casey Xu, FDA 

Keywords: Phase I clinical trial, oncology, safety, Bayesian

The objective of a Phase I trial in oncology usually is to find the maximum tolerated dose (MTD) to be used in later phases of drug development. In recent times many new designs, other than the traditional 3+3 design, that use Bayesian continual reassessment method (CRM) and its modifications, Bayesian logistic regression and also frequentist methods that use isotonic regression have been proposed. In general these designs try to minimize the sample size and reach the MTD as quickly as possible which may be unsafe for the trial subjects. Safety of the trial subjects is a very important aspect from a regulatory perspective while studying the new drugs for the first time in humans. We will discuss regulatory experience in oncology with some of these methods and what precautions are needed to avoid exposing the subjects to unsafe doses while using rapid dose escalation Phase I designs.