Investigational new drugs
-
Investigational new drugs · Feb 2010
Two-stage model-based clinical trial design to optimize phase I development of novel anticancer agents.
The phase I program of anticancer agents usually consists of multiple dose escalation studies to select a safe dose for various administration schedules. We hypothesized that pharmacokinetic and pharmacodynamic (PK-PD) modeling of an initial phase I study (stage 1) can be used for selection of an optimal starting dose for subsequent studies (stage 2) and that a post-hoc PK-PD analysis enhances the selection of a recommended dose for phase II evaluation. The aim of this analysis was to demonstrate that this two-stage model-based design, which does not interfere in the conduct of trials, is safe, efficient and effective. ⋯ A two-stage model-based phase I design is safe for anticancer agents with dose-limiting myelosuppression and may enhance the efficiency of dose escalation studies by reducing the number of patients treated with a dose below the recommended dose and by increasing the precision of dose selection for phase II evaluation.