Fifteen years of pediatric neuro-oncology trials: Insights from ClinicalTrials.gov to optimize future design

Abstract Background Pediatric brain tumors are the leading cause of cancer-related mortality in children. Despite therapeutic advances, outcomes remain poor, and trial conduct is challenged by disease rarity, limited accrual pools, and complex multimodal regimens. Premature trial termination compounds these challenges, wasting resources and delaying progress. A comprehensive evaluation of the US pediatric neuro-oncology trial landscape and determinants of early discontinuation has not been performed. Methods We queried ClinicalTrials.gov for US-based interventional pediatric neuro-oncology trials initiated between January 1, 2010, and December 31, 2024. Trials were categorized by design features, tumor type, sponsor, and consortium involvement. Temporal trends, trial duration, and reasons for discontinuation were analyzed. Multivariable Cox proportional hazards models assessed factors associated with trial completion among trials initiated between 2010 and 2019. Results Of 819 identified trials, 243 met inclusion criteria. Most trials were early phase (phase 1/1-2, 69.5%) and focused on recurrent/progressive disease (68.3%), with targeted therapy (53.9%) and immunotherapy (26.3%) most common. Trial opening declined significantly over time (Poisson regression, P < .001), although the proportion of closed trials remained stable (χ² P = .97). Mean time to accrual was 4.8 ± 1.2 years, with modest improvement after 2018. Among 52 (21.4%) prematurely closed trials, poor accrual was the leading reason (50%), followed by funding issues (19.2%). Multivariable analysis identified greater site numbers decreasing the risk of premature discontinuation (hazard ratio = 0.55; 95% CI, 0.35-0.83). Conclusions Multisite reach is a key determinant of trial persistence. Strategies to optimize accrual and reduce early termination should prioritize interinstitutional networks and trial platform site networks.