Immunotherapy for Brain Tumor

Not currently recruiting at 499 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Checkpoint inhibitors, Bevacizumab

Disqualifiers: Autoimmune diseases, Active malignancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 13

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of two immunotherapy drugs, ipilimumab (Yervoy) and nivolumab (Opdivo), in treating recurrent gliomas with numerous genetic changes. These drugs may enhance the immune system's ability to combat cancer and prevent its growth or spread. Individuals with recurrent glioblastoma, characterized by a high number of mutations and no prior treatment with similar immunotherapies, may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's efficacy in an initial, smaller group of participants.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that the combination of nivolumab and ipilimumab has been tested in patients with melanoma, including those with brain metastases. The combination did not reveal any new safety concerns. However, about 55% of patients experienced serious side effects, with 7% having effects on the brain and nervous system. This indicates that some people had significant reactions, but these were mostly known or expected.

Although this information comes from studies on other types of cancer, the same combination is being tested for brain tumors in this trial. Knowing the trial phase is helpful. As a Phase 2 trial, there is already some safety information from earlier studies. However, monitoring how participants react in this specific trial remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ipilimumab and nivolumab for brain tumors because these treatments take a novel approach by harnessing the power of the immune system, unlike traditional therapies like surgery, radiation, or chemotherapy. Ipilimumab and nivolumab are immune checkpoint inhibitors that work by blocking proteins that prevent T-cells from attacking cancer cells, allowing the immune system to target the tumor more effectively. This mechanism offers a promising alternative to existing treatments, potentially leading to improved outcomes for patients with brain tumors.

What evidence suggests that this treatment might be an effective treatment for recurrent glioma?

Research has shown that using the immunotherapy drugs ipilimumab and nivolumab together can treat certain cancers more effectively. In this trial, participants will receive both ipilimumab and nivolumab. Studies have found that this combination improves patient response to treatment and increases survival rates, especially in those with cancer that has spread to the brain. For patients with melanoma and untreated brain cancer, this drug duo has remained effective for several years. This suggests it might also work for recurrent glioma, a type of brain tumor with many mutations. These drugs help the immune system attack and possibly stop these tumors from growing and spreading. ^{5 6 7 8 9}

Who Is on the Research Team?

Gavin P Dunn

Principal Investigator

Alliance for Clinical Trials in Oncology

Are You a Good Fit for This Trial?

Adults (18+) with recurrent glioma, specifically high-grade glioblastomas or astrocytomas at first or second recurrence. Participants must have measurable disease on MRI and not be on high doses of steroids. No history of autoimmune diseases, no prior immunotherapy or bevacizumab, and should meet certain blood test criteria for organ function.

Inclusion Criteria

REGISTRATION ELIGIBILITY CRITERIA: Tissue obtained from biopsy or resection at first or second recurrence exhibits TMB >= 10 on FoundationOne CDx testing

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nivolumab and ipilimumab intravenously. Treatment repeats every 3 weeks for 4 cycles, followed by nivolumab every 4 weeks.

16 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs every 8 weeks until disease progression, then every 3 months for up to 3 years.

Up to 3 years

Regular visits every 8 weeks, then every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• Nivolumab

Trial Overview The trial is testing the effectiveness of two immunotherapy drugs, Ipilimumab and Nivolumab, in patients with a type of brain tumor called glioma that has returned after treatment. The study focuses on tumors with a high number of genetic mutations to see if these drugs can help the immune system fight cancer better than current treatments.

How Is the Trial Designed?

Group I: Treatment (nivolumab, ipilimumab) Experimental Treatment 3 Interventions

Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 30 minutes on day 1. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI throughout the study.

Ipilimumab is already approved in United States, European Union for the following indications:

Approved in United States as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Approved in European Union as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11275236/

Efficacy of Ipilimumab and Nivolumab in Patients with ... These studies showed that the combination of immunotherapy with ipi/nivo increased clinical response and survival of patients with asymptomatic ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.2619

A multi-center basket trial analysis (NCI/SWOG S1609). We report outcomes in patients with BM from the largest basket trial for rare cancers (N=684 evaluable patients) to evaluate efficacy and ...

3. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(24)00735-6/abstract

7-year follow-up of a multicentre, open-label, randomised ... Our findings suggest that ipilimumab plus nivolumab maintains efficacy to at least 7 years in patients with active asymptomatic brain metastasis ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1805453

Combined Nivolumab and Ipilimumab in Melanoma ... We evaluated the efficacy and safety of nivolumab plus ipilimumab in patients with melanoma who had untreated brain metastases.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11968462/

Timing of brain metastases in relation to outcome during first ... Ipilimumab and nivolumab therapy of patients with MBM at diagnosis was associated with a modest overall benefit in progression-free survival ( ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8563325/

Safety and efficacy of the combination of nivolumab plus ... In patients with melanoma and asymptomatic brain metastases (MBM), nivolumab plus ipilimumab provided an intracranial response rate of 55%.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1470204524007356

Ipilimumab plus nivolumab versus nivolumab alone in ... Most recently in 2024, NIBIT-M2 reported a 7-year overall survival of 43% with ipilimumab plus nivolumab, compared with 10% for the two groups receiving ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e14001

Real-world outcomes in patients with brain metastases ... Thirty-nine patients had brain metastasis at the time of nivo-rela initiation. Most patients (30 of 44 [68.2%]) had 1-3 MBM, while (14 of 44 [ ...

9. jto.org jto.org/article/S1556-0864(23)00525-7/fulltext

Systemic and Intracranial Outcomes With First-Line ... No new safety signals were observed in patients with or without baseline brain metastases treated with nivolumab plus ipilimumab. These data ...