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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether nivolumab, an immunotherapy drug, can delay or avoid radiation treatment for individuals with a specific type of brain cancer called RRD-glioblastoma. The study examines tumor changes with this treatment and includes two parts: one with nivolumab alone and another combining it with radiation if the cancer progresses. Suitable candidates for this trial are those who have undergone surgery to remove most or all of their glioblastoma tumor and meet specific immune and genetic markers. As an unphased trial, this study offers patients the chance to contribute to groundbreaking research that could lead to new treatment strategies.

Do I need to stop my current medications for the trial?

The trial requires that you stop taking systemic corticosteroids or other immunosuppressive therapies at least 7 days before starting the trial. If you are on other anti-cancer agents, you will need to stop those as well. The protocol does not specify other medications, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that nivolumab is generally safe for people. One study found that when used alone, nivolumab did not introduce new safety issues for patients with brain tumors. Patients tolerated it well, experiencing side effects similar to those from other treatments for similar conditions. Another study found that combining nivolumab with radiation is also safe. This combination did not cause unexpected side effects, and the number of neurological problems was similar to what is typically seen with this disease. Overall, current data suggests that nivolumab, both alone and with radiation, is well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for brain tumors, like surgery, chemotherapy, and radiation, focus on directly attacking the tumor cells. But nivolumab works differently. It is an immunotherapy drug that helps your immune system recognize and fight the tumor more effectively. Researchers are excited about the combination of nivolumab with radiation because this approach has the potential to enhance the body's natural defenses while directly targeting tumor cells with radiation. This dual attack strategy might offer improved outcomes over traditional treatments.

What evidence suggests that this trial's treatments could be effective for RRD-glioblastoma?

Research has shown that nivolumab may improve survival rates for people with glioblastoma, a type of brain tumor. Studies have found that nivolumab can reach brain tumors and help the immune system's T-cells attack cancer cells. However, when used alone, nivolumab hasn't consistently outperformed other treatments, such as bevacizumab. In this trial, participants in Domain 1 will receive nivolumab upfront, while those in Domain 2 will receive a combination of radiation and nivolumab followed by maintenance nivolumab. Combining nivolumab with radiation therapy has shown better results, with some studies noting an increase in survival from 12.1 to 14.6 months. This suggests that using nivolumab with radiation might be beneficial for treating brain tumors like glioblastoma. ^{1 2 6 7 8}

Who Is on the Research Team?

Daniel Morgenstern, MD

Principal Investigator

The Hospital for Sick Children

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Anti Cancer Fund

Collaborator

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37503551/

Nivolumab for newly and recurrent glioblastoma multiforme ... After conducting a thorough analysis, our meta-analysis indicated that treatment with Nivolumab led to improved overall survival (OS) outcomes ...

2. aacrjournals.org aacrjournals.org/cancerimmunolres/article/12/9/1202/747081/Nivolumab-Reaches-Brain-Lesions-in-Patients-with

Nivolumab Reaches Brain Lesions in Patients with Recurrent ... Our study demonstrates that nivolumab does reach the GBM tumor lesion and enhances antitumor T-cell responses both intratumorally and systemically. However, ...

3. nature.com nature.com/articles/s41423-024-01226-x

Immunotherapy for glioblastoma: current state, challenges ... Despite these aggressive treatments, the median overall survival (mOS) of GBM patients remains dismally low, typically ranging from 12–18 months ...

4. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2766213

Effect of Nivolumab vs Bevacizumab in Patients With ... Meaning Additional research is needed; nivolumab monotherapy did not improve overall survival compared with bevacizumab in the treatment of ...

5. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1582296/full

An update on the clinical trial research of immunotherapy ... For newly diagnosed glioblastoma, phase II RCT data indicate a median survival of 10.1 months with pembrolizumab plus SOC (NCT03018288), though ...

6. ascopubs.org ascopubs.org/doi/10.1200/jco.2014.32.15_suppl.tps2101

Randomized phase IIb study of nivolumab (anti-PD-1 We present a phase IIb, randomized, open-label study to evaluate the efficacy and safety of nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11369628/

Nivolumab Reaches Brain Lesions in Patients with Recurrent ... Our study demonstrates that nivolumab does reach the GBM tumor lesion and enhances antitumor T-cell responses both intratumorally and systemically. However, ...

8. news.bms.com news.bms.com/news/details/2017/First-Presentation-of-Efficacy-Data-from-CheckMate--204-Evaluating-the-Combination-of-Opdivonivolumab-and-Yervoyipilimumab-Demonstrates-Anti-tumor-Activity-in-Advanced-Melanoma-Patients-with-Brain-Metastases/default.aspx

First Presentation of Efficacy Data from CheckMate -204 ... Over half of patients (55%) experienced an intracranial objective response with 21% achieving a complete intracranial response Bristol-Myers Squibb Company ...