Exploring the causes of failures in oral leukoplakia clinical trials.

Abstract

e18087 Background: A proportion of oral cancers arise from oral leukoplakia (OL), a disorder characterized by white plaques with variable malignant transformation rates. Despite advances in medical research, effective, evidence-based interventions remain limited, with high recurrence rates and no standardized first-line treatment. This study investigates the underlying causes of failed clinical trials (CTs) targeting OL interventions, aiming to provide insight for future successful trials. Methods: We identified intervention-type CTs for OL using the term "leukoplakia," between 1998 and 2023 using ClinicalTrials.gov. CTs were categorized into “cases” (withdrawn/terminated, failed, or of unknown status) and “controls" (completed trials with published results). CTs addressing conditions such as erythroplakia, lichen planus, and oral hairy leukoplakia were excluded. Data collected included trial phase, intervention type, subject accrual rates, reasons for trial failure, and sponsorship characteristics. Results: A total of 38 CTs were identified; 16 cases and 5 controls met inclusion criteria. Among the cases, 56.3% were randomized controlled trials (RCTs), while in the controls 60% RCTs. Recruitment and enrollment challenges were the leading cause of failure (31.3%), followed by efficacy and safety concerns (25%). Failed OL CTs (cases) were more likely to have government sponsorship (50% vs. 20%) and lower average accrual rates (67% vs. 97.5%) compared to completed trials (controls). Phase 1 failed CTs achieved 26% of projected accrual, whereas Phase 2 trials reached 79%. Control CTs in both Phase 1 and Phase 2 achieved 86% and 98% accrual, respectively. Intervention types among failed trials were varied, including pioglitazone (19%), celecoxib (13%), and photodynamic therapy (13%). Control trial interventions were predominantly investigating photodynamic therapy (40%). Conclusions: We found that completed and successful OL trials were more likely to have higher accrual rates and were predominantly sponsored by government (50%), whereas academic-sponsored trials constituted the next largest proportion of failed trials (31.3%). Recruitment and enrollment challenges emerged as the leading cause of failure, highlighting the need for improved participant engagement strategies and realistic recruitment targets in future studies. Moreover, the diversity of interventions tested underscores the demand for standardized treatment. Failure reasons and sponsorship. Reason for Failure Phase I Phase II Phase III N/A Total Recruitment/Enrollment 2 2 0 0 4/16 (25%) Efficacy/Safety 1 3 0 1 5/16 (31.3%) Investigator/Site Issues 2 1 0 0 3/16 (18.8%) No Published Results 0 2 1 1 4/16 (25%) Sponsorship Type  Academic 1 1 1 2 5/16 (31.3%)  Governmental 2 6 0 0 8/16 (50%)  Private 0 1 0 0 1/16 (6.3%)  Industry 2 0 0 0 2/16 (12.5%)