Outcome of children and adolescents with central nervous system tumors in phase I trials

Abstract

Central nervous system (CNS) tumors are a leading cause of death in pediatric oncology. New drugs are desperately needed to improve survival. We evaluated the outcome of children and adolescents with CNS tumors participating in phase I trials within the Innovative Therapies for Children with Cancer (ITCC) consortium. Patients with solid tumors aged < 18 years at enrollment in their first dose-finding trial between 2000 and 2014 at eight ITCC centers were included retrospectively. Survival was evaluated using univariate/multivariate analyses. Overall, 114 patients were included (109 evaluable for efficacy). Median age was 10.2 years (range 1.0-17.9). Main diagnoses included: medulloblastoma/primitive neuroectodermal tumors (32.5%) and high-grade gliomas (23.7%). Complete/partial responses (CR/PR) were reported in 7.3% patients and stable disease (SD) in 23.9%. Performance status of 90-100%, school/work attendance, normal ALT/AST and CR/PR/SD correlated with better overall survival (OS) in the univariate analysis. No variables assessable at screening/enrollment were associated with OS in the multivariate analysis. Five patients (4.5%) were discontinued from study due to toxicity. No toxic deaths occurred. Median OS was 11.9 months with CR/PR, 14.5 months with SD and 3.7 months with progressive disease (p < 0.001). The enrollment of children and adolescents with CNS tumors in phase I trials is feasible, safe and offers potential benefit for the patients. Sustained disease stabilization has a promising role as a marker of anti-tumor activity in children with CNS tumors participating in phase I trials.

Evolution of the Innovative Therapies for Children With Cancer Consortium Trial Portfolio for Drug Development for Children With Cancer

“…ITCC is a founder partner of the ACCELERATE international multistakeholder platform. 7 Over the past two decades, ITCC has supported an expedited drug development process for childhood cancers through promotion of improved trial methodology, [8][9][10][11][12] reanalysis/ meta-analysis of trial data, [13][14][15][16][17][18][19] and multistakeholder collaborations (eg, ACCELERATE platform 7 ), which remain extremely valuable to the global drug development community. 20 We report an analysis of all phase I to II trials conducted by ITCC between 2003 and 2018, focusing on the evolution of trial metrics over time.…”

“…Over the past two decades, ITCC has supported an expedited drug development process for childhood cancers through promotion of improved trial methodology, 8-12 reanalysis/meta-analysis of trial data, 13-19 and multistakeholder collaborations (eg, ACCELERATE platform 7 ), which remain extremely valuable to the global drug development community. 20…”