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)

Sponsor
Daniel Morgenstern
Study ID
NCT06519682
Status
Recruiting
Apply to this trial

Conditions

  • High Grade Glioma
  • Replication Repair Deficient

Eligibility Criteria

Sex
ALL
Age
12 Months - 25 Years
Healthy Volunteers
Not accepted

Interventions

  • Nivolumab — DRUG
    All patients will be administered Nivolumab with or without radiation
  • Radiation — RADIATION
    Radiation

Study Details

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.

Key Dates

Start date
Dec 6, 2024
Status verified
Aug 2025
Primary completion
Dec 31, 2026
Completion
Aug 31, 2029

Study Design

Enrollment
20 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Active Comparator: Domain 1 - Upfront ICI
    Initially 12 eligible patients will be enrolled for upfront ICI. At 12 week assessment if \>6 patients have response (NO radiation for recurrence/progression), an additional 6 patients will be enrolled for upfront ICI. All patients will be assessed at 12 weeks from the start of ICI. If 6 or fewer patients have response (NO radiation for progression/recurrence), no more patients will be recruited to this domain.
  • Active Comparator: Domain 2 - Radiation + ICI → maintenance ICI
    All the patients experiencing tumor progression on domain 1 will be eligible for domain 2 and will receive a combination of radiation and nivolumab followed by maintenance nivolumab for 2 years. To be eligible for domain 2 post recurrence patients will need surgery/biopsy at recurrence. If 6 RRD-glioblastoma will recur/progress at 12 weeks on domain 1 then 8 additional eligible patients may be directly enrolled in domain 2.

Primary Outcome Measure

To evaluate Radiation-free survival (RFS) from start of immunotherapy [ Time Frame: 2 years ]

Central Contacts

Related Studies