A two-stage algorithm for designing phase I cancer clinical trials for two new molecular entities.

摘要

The continual reassessment method (CRM) and subsequent developments of the Bayesian approach provide important tools for the design of Phase I cancer clinical trials for a new molecular entity. In recent years the idea of developing a treatment composed of two molecular entities has been proposed. For example, for some tumor types there may be two signaling pathways, both of which need to be blocked simultaneously using two molecules to achieve therapeutic benefit. A two-stage Bayesian and likelihood based algorithm is introduced herein for designing Phase I cancer clinical trials for two new molecular entities. It starts with a modified CRM approach in the first stage and makes use of the accumulated data from the first stage to provide likelihood estimates of model parameters for use in the second stage.