Pilot Study of Upfront Immunotherapy With Nivolumab in Children, Adolescents, and Young Adults Aged 1 to 25 With Replication-Repair Deficient High-Grade Gliomas

What this Trial Is About

This research focuses on children, adolescents, and young adults aged 12 to 25 years with replication-repair deficient RRD high-grade gliomas, specifically glioblastoma. The study aims to evaluate the use of an immune checkpoint inhibitor ICI, nivolumab, given upfront to delay or avoid radiation in patients with favorable immune and genomic biomarkers, including those with gross total or near total tumor resection. This pilot study is open-label and multicenter, designed to explore tumor response and evolution under immunotherapy treatment. The study has two parts. In the first part, 12 patients receive nivolumab every 4 weeks and are assessed at 12 weeks if more than half respond without needing radiation, 6 more patients join this group. In the second part, patients whose tumors progress after the first phase undergo surgery or biopsy and then receive radiation combined with nivolumab, followed by maintenance nivolumab for up to 2 years. Patients can be treated for about 2 years total, with follow-up continuing up to one year after treatment ends. Participants will have regular assessments including scans and biopsies to monitor tumor status and immune response. Researchers will measure how long patients avoid radiation after starting immunotherapy and track overall survival, progression-free survival, clinical benefit, and quality of life over time. Safety monitoring and long-term follow-up are included to understand treatment effects and tumor changes during and after therapy.

A Pilot Study Investigating Upfront Adaptive Immunotherapy Approach in Children, Adolescent and Young Adult (CAYA) Patients With Replication-Repair Deficient (RRD) High-Grade Gliomas (HGG)