Early Trial Discontinuation in Toxicity-Driven, Dose-Escalating, Phase I Cancer Trials: Occurrence, Outcomes and Predictive Factors

The selection of patients for phase I cancer trials remains challenging. Patients who dropout of the trial before completion need to be replaced and this can result in significant delays to trial completion. The objective of this study was to identify patients enrolled in phase I oncology trials who were unable to complete the minimum evaluation period of the trial, and to use these data to develop a predictive model of risk factors for patient replacement. We retrospectively reviewed all consecutive patients who were enrolled in dose-escalating phase I cancer trials at four medical centers in France between May 2003 and May 2013. Replacement was defined as trial discontinuation before 6 weeks, without the occurrence of dose-limiting toxicity. Using logistic regression and decision-tree analyses, we developed a predictive model to identify patients who were at high risk for replacement, and also their common risk factors. This model was designed to provide maximum specificity and a negative predictive value. Of 332 patients enrolled in the study, 16 had to be replaced (4.8 %). The median overall survival time was 45 days for the patients who were replaced versus 480 days for the patients who were not replaced (p