Nivolumab + Radiation for Brain Tumor

Overseen By Nirav Thacker, MD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Daniel Morgenstern

Must not be taking: Corticosteroids, Anti-cancer agents

Disqualifiers: Autoimmune disease, Interstitial lung disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 3

20 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Research Team

Daniel Morgenstern, MD

Principal Investigator

The Hospital for Sick Children

Eligibility Criteria

This trial is for children, adolescents, and young adults aged between 1 to 25 years with high-grade gliomas that are replication-repair deficient. They must have had a major surgery to remove the tumor and show certain immune markers. Prior chemotherapy should be completed at specific intervals before starting this trial.

Inclusion Criteria

I am between 1 year and 25 years old.

I have recovered from side effects of past cancer treatments, except for hair loss and low lymphocyte count.

This criterion seems to be a reference number and does not provide information.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Upfront ICI

Participants receive upfront immune checkpoint inhibitor (ICI) therapy with nivolumab to delay/avoid radiation

12 weeks

3 visits (in-person, every 4 weeks)

Radiation + ICI

Participants experiencing tumor progression receive a combination of radiation and nivolumab followed by maintenance nivolumab

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Treatment Details

Interventions

• Nivolumab

Trial Overview The study tests nivolumab as an initial treatment in patients with favorable biomarkers to potentially delay or avoid radiation therapy. At tumor progression, participants will receive both radiation and nivolumab followed by maintenance doses of nivolumab.

Participant Groups

Group I: Domain 1 - Upfront ICI Active Control 1 Intervention

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.

Group II: Domain 2 - Radiation + ICI → maintenance ICI Active Control 2 Interventions

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.

Who Is Running the Clinical Trial?

Daniel Morgenstern

Lead Sponsor

Trials

2

Recruited

80+