Characterization of terminated and withdrawn clinical trials for the treatment and prevention of oral mucositis.

Purpose: Oral mucositis (OM) is a significant complication of cytotoxic cancer therapy and has no effective therapies. Unfortunately, the termination rate of clinical trials (CTs) testing potential OM interventions remains high. Here, we compared the characteristics of failed trials and matched completed trials to identify common features, which might inform better study design.

Methods: CTs for the prevention/treatment of OM were identified using ClinicalTrials.gov. Failed (terminated or withdrawn) trials were evaluated for phase, type of cancer treatment (radiotherapy, chemotherapy, or chemo-radiotherapy), subject accrual, study type, number of clinical sites, intervention type, inclusion criteria, sponsor type, and reason(s) for failure. A secondary analysis of completed OM CTs that were individually matched to failed trials based on indication and phase or intervention type served as a control.

Results: Failed OM CTs were more likely to have academic sponsorship (45.7% vs. 39.1%), nonrandomized design (19.6% vs. 4.3%), and lower mean subject accrual (27.8 subjects vs. 101.4 subjects) compared to completed trials. The leading reason for termination was recruitment/enrollment (37.9%). Recruitment/enrollment and safety/efficacy accounted for failure in 84.6% of phase II trials.

Conclusion: Contrary to general CTs where safety/efficacy concerns predominate, our results suggest OM-related trial failures are associated with a broader list of challenges including recruitment/enrollment, funding/sponsorship, and investigator/site issues. OM CTs demand aggressive planning, funding, and careful selection of trial sites and sponsorship to assure timely subject recruitment and reduce the risk for early termination and withdrawal.