Actively Recruiting
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)
Led by Daniel Morgenstern · Updated on 2025-08-29
20
Participants Needed
1
Research Sites
242 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 is open label, multicentre, single arm, pilot study of upfront nivolumab in patients with RRD-glioblastoma with favorable immune/genomic biomarkers. The purpose of the study is to use upfront immune checkpoint inhibitor (ICI) to delay/avoid radiation for patients with RRD-glioblastoma with favorable clinical (Gross total resection (GTR) or near total resection (NTR)) and biological (RRD, hypermutation, immune activation) biomarkers. At progression, patients will be undergoing surgery/biopsy and will get a combination of radiation + ICI followed by maintenance ICI. This model will allow us to additionally study the evolution tumor in response to ICI. The study will have two domains.
CONDITIONS
Official 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...
- Patients must be between 12 months and 25 years old at the time of consent.
- Histologically confirmed diagnosis of glioblastoma.
- Proof of replication-repair deficiency by tumor testing or prior germline genetic testing.
- Availability of tumor tissue specimen for molecular profiling.
- Favorable immune markers including high PD1 and CD8 positivity.
- Gross total resection (GTR) or near total resection (NTR) confirmed by post-surgery scan.
- Ability to start therapy within 4 weeks of last surgery.
- Recovery from acute toxic effects of prior anti-cancer therapies except alopecia and lymphopenia.
- Prior therapy with nivolumab or other PD-1/PD-L1 inhibitors allowed only if for tumors other than high-grade glioma.
- No prior therapy for high-grade glioma except surgery.
- Adequate performance status (Lansky score ≥50 if ≤16 years; Karnofsky score ≥50 if >16 years).
- Adequate bone marrow, renal, liver, pulmonary, cardiac, and pancreatic function.
- HIV, HBV, or HCV infection allowed if controlled as specified.
- Ability to understand and willingness to provide informed consent or assent.
You will not qualify if you...
- Use of systemic corticosteroids or other immunosuppressive therapy within 7 days prior to protocol therapy start.
- Concurrent use of other anti-cancer agents.
- Use of other investigational agents within 14 days prior to protocol therapy.
- CNS tumors with uncal herniation, severe midline shift, or significant mass effect after surgery.
- Uncontrolled intercurrent illness including active infection, severe heart failure, unstable angina, arrhythmia, or psychiatric/social situations limiting compliance.
- Pregnant or breastfeeding females.
- History of autoimmune disease requiring systemic treatment within 2 years prior to therapy.
- History of interstitial lung disease or pneumonitis.
- Previous solid organ or allogenic stem cell transplant.
- Previous grade 4 or life-threatening reaction to nivolumab or PD-1/PD-L1 antibodies.
- Inability to comply with safety monitoring.
- Inability to start protocol treatment within 14 days of enrollment or within 4 weeks of surgery.
- For Domain 2, inability to have surgery/biopsy at recurrence or tumors ≥5cm or causing severe mass effect at progression.
AI-Screening
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Trial Site Locations
Total: 1 location
1
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Actively Recruiting
Research Team
N
Nirav Thacker, MD
CONTACT
A
Aiman Siddiqi
CONTACT
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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