Dose finding trials in pediatric oncology

Dr. Arzu Onar-Thomas

Arzu Onar-Thomas, PhD

Pediatric phase I trials differ substantially ways from their adult counterparts and thereby pose unique challenges. A notable complexity arises during the dosing of oral agents, which is often based on body surface area in children. Given the fixed pill sizes and nonavailability of pediatric formulations, the use of oral agents in pediatric phase I trials requires special monitoring to ensure patient safety and estimating the maximum tolerated dose (MTD). Model-based designs such as the continual reassessment method (CRM) can be especially helpful in such settings. On the other hand because the adult MTD is usually available at the time of a corresponding pediatric trial, the range of doses studied in pediatric phase I trials is typically limited and the challenges of rapidly identifying the MTD and minimizing treatment at sub-therapeutic doses are not as pressing. Herein, we discuss adaptations to various dose finding approaches that are needed to enable their use in multi-institutional pediatric phase I trials. We also provide anecdotes from actual trials conducted by the Pediatric Brain Tumor Consortium during the past 15 years that highlight the unique characteristics of early phase pediatric studies.

Full Citation

Onar-Thomas A and Thomas F. Dose-finding trials in pediatric oncology. In: O’Quigley J, Iasonos A, Bornkamp B (eds). Handbook of Methods for Designing, Monitoring, and Analyzing Dose-Finding Trials. Boca Raton, FL: Chapman and Hall/CRC, 2017.