Actively Recruiting
U-R-Immune Glioma (CA209-1245): A Pilot Study Investigating Upfront Adaptive Immunotherapy in Children, Adolescents, and Young Adults With Replication-Repair Deficient High-Grade Gliomas
Led by Daniel Morgenstern · Updated on 2025-08-29
20
Participants Needed
1
Research Sites
139 weeks
Total Duration
On this page
Sponsors
D
Daniel Morgenstern
Lead Sponsor
C
Canadian Institutes of Health Research (CIHR)
Collaborating Sponsor
AI-Summary
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.
CONDITIONS
Brief Title
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)
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age between 12 months and 25 years at consent
- Histologically confirmed diagnosis of glioblastoma
- Evidence of replication-repair deficiency by tumor testing or germline testing
- Provide tumor tissue specimen for molecular profiling including tumor mutational burden analysis
- High PD1 and CD8 immune markers as specified
- Gross total resection or near total resection confirmed by post-surgery scan
- Able to start therapy within 4 weeks of last surgery
- Recovered from acute toxic effects of prior anti-cancer therapies (except alopecia and lymphopenia)
- No prior therapy except surgery for high-grade glioma
- Performance status score of at least 50 (Lansky if ≤16 years, Karnofsky if >16 years)
- Adequate bone marrow, renal, liver, pulmonary, cardiac, and pancreatic function
- HIV, Hepatitis B or C infection allowed if viral loads controlled or cured
- Ability and willingness to provide informed consent or assent as appropriate
You will not qualify if you...
- Use of systemic corticosteroids or immunosuppressive therapy within 7 days before starting study treatment
- Current use of other anti-cancer agents
- Use of other investigational agents within 14 days before starting treatment
- CNS tumors with uncal herniation or severe midline shift or significant mass effect after surgery
- Uncontrolled intercurrent illness including active infection, severe heart failure, unstable angina, arrhythmia, or psychiatric/social conditions limiting compliance
- Pregnant or breastfeeding females; females of reproductive potential must have negative pregnancy test and agree to contraception
- History of autoimmune disease requiring systemic treatment within 2 years
- History of interstitial lung disease or pneumonitis
- Previous solid organ or allogenic stem cell transplant
- Previous life-threatening or severe reaction to nivolumab or PD-1/PD-L1 inhibitors
- Unable to comply with safety monitoring requirements
- Unable to start study treatment within 14 days of enrollment or 4 weeks of surgery
- For domain 2: unable to have surgery/biopsy at recurrence, tumor size ≥5 cm, or significant mass effect at progression
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - 12 weeks
Participants receive Nivolumab every 4 weeks for an initial 12-week period (3 cycles) to assess response without radiation.
3 visits (in-person, every 4 weeks)
Duration - Up to 2 years
Participants who experience tumor progression after upfront immunotherapy receive a combination of radiation and Nivolumab followed by maintenance Nivolumab treatment for up to 2 years.
24 visits (in-person, every 4 weeks during maintenance)
Duration - Up to 1 year
After completing treatment, participants are followed for up to one year to monitor health and outcomes.
Periodic visits as scheduled by the study team
Trial Site Locations
Total: 1 location
1
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Actively Recruiting
Research Team
N
Nirav Thacker, MD
A
Aiman Siddiqi
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
2
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