Application of the patient-reported outcomes continual reassessment method to a phase I study of radiotherapy in endometrial cancer

This article considers the concept of designing Phase I clinical trials using both clinician- and patient-reported outcomes to adaptively allocate study participants to tolerable doses and determine the maximum tolerated dose (MTD) at the study conclusion. We describe an application of a Bayesian form of the patient-reported outcomes continual reassessment method (PRO-CRMB) in an ongoing Phase I study of adjuvant hypofractionated whole pelvis radiation therapy (WPRT) in endometrial cancer (NCT04458402). The study’s primary objective is to determine the MTD per fraction of WPRT, defined by acceptable clinician- and patient-reported DLT rates. We conduct simulation studies of the operating characteristics of the design and compared them to a rule-based approach. We illustrate that the PRO-CRMB makes appropriate dose assignments during the study to give investigators and reviewers an idea of how the method behaves. In simulation studies, the PRO-CRMB demonstrates superior performance to a 5 + 2 stepwise design in terms of recommending target treatment courses and allocating patients to these courses. The design is accompanied by an easy-to-use R shiny web application to simulate operating characteristics at the design stage and sequentially update dose assignments throughout the trial’s conduct.