Strategic roadmap for delivery of clinical trials in rare childhood central nervous system (CNS) tumours: a multi-stakeholder consensus
Abstract
Abstract Rare paediatric central nervous system (CNS) tumours comprise a biologically-heterogeneous group of low-incidence diseases that present significant challenges to both therapeutic development and clinical research, limiting the availability of high-quality evidence to guide clinical care. The UK3CR Children’s Cancer Research Group (CRG) CNS Tumours Subgroup convened a multidisciplinary workshop to identify research priorities and establish a strategic framework for advancing clinical trials in this setting. Four high-priority tumour groups—craniopharyngioma, choroid plexus carcinoma (CPC), very high-risk medulloblastoma (VHR-MB), and rare embryonal and sarcomatous tumours (REST), including embryonal tumour with multilayered rosettes (ETMR)—were evaluated. Key outcomes included the feasibility of a UK-led craniopharyngioma trial, the need for enhanced national CPC data collection, and support for European early-phase platform trials in VHR-MB. REST highlighted transnational regulatory complexity requiring coordinated registries and parallel trial models. Cross-cutting barriers included regulatory discordance, contracting delays, fragmented funding, pharmacovigilance differences, data-sharing constraints, and interoperable infrastructures. The workshop emphasised innovative methodologies, including Bayesian/adaptive designs, platform trials, and external control arms, to maximise efficiency in small populations, alongside strengthened patient involvement and international collaboration. Collectively, these findings define a collaborative and internationally-aligned strategic roadmap to accelerate clinical research and improve outcomes in rare paediatric CNS tumours.
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Authors: Jenny Adamski, John Apps, Sarita Depani, Rebecca M. Hill, B Pizer, Thankamma Ajithkumar, Simon Bailey, Kim S. Bull, Fernando Carceller, Julia Cockle, Robert A. Dineen, Jessica A. Douglas‑Pugh, Jenny Gains, Debbie Hicks, Mette Jorgensen, John‐Paul Kilday, Juan Pedro Martı́nez-Barberá, Timothy Ritzmann, Emma Thompson, Simon Gates, Darren Hargrave, Allan Hackshaw, G.A. Amos Burke, Steven C. Clifford
Institutions: University of Liverpool, University of Manchester, Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham Biomedical Research Centre, University College London, Manchester Academic Health Science Centre, Cancer Research UK, University of Birmingham, Great Ormond Street Hospital, Newcastle University, University of Southampton, Royal Marsden NHS Foundation Trust, Cambridge University Hospitals NHS Foundation Trust, Institute of Cancer Research, Manchester University NHS Foundation Trust, Cancer Research UK Clinical Trials Unit, Brain Tumour Charity, Great Ormond Street Hospital for Children NHS Foundation Trust, University College London Hospitals NHS Foundation Trust, Birmingham Women’s and Children’s NHS Foundation Trust