Nivolumab + Radiosurgery for Recurrent Meningioma

Not currently recruiting at 32 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Anti-PD-1, Anti-CTLA-4, others

Disqualifiers: Chemotherapy, Radiation, Autoimmune, Transplant, 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: 2

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of treatments for individuals with grade II-III meningioma that has recurred after previous radiation therapy. The researchers aim to explore the effectiveness and safety of the drug nivolumab (an immunotherapy drug), alone or combined with another immunotherapy drug, ipilimumab, when paired with a focused radiation therapy called stereotactic radiosurgery. This trial is suitable for those previously treated for meningioma who have measurable tumor growth. Participants will receive either nivolumab and radiosurgery or a combination of nivolumab, ipilimumab, and radiosurgery. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking advancements in meningioma treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently using immunosuppressive medication, except for certain types like inhaled or topical steroids, or if you have had chemotherapy within 4 weeks before the study.

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

Research shows that stereotactic radiosurgery (SRS) is generally safe for treating brain tumors like meningiomas, though it may carry a higher risk of side effects compared to other treatments. Studies have found that adding nivolumab, a drug that boosts the immune system, to radiosurgery is usually well-tolerated by patients with recurring meningiomas.

Less information is available when nivolumab is combined with ipilimumab, another immune-boosting drug, and used with radiosurgery. However, current research suggests this combination can be safe for patients. These treatments are being tested to determine the best way to use them together, so researchers are still learning about their safety.

In summary, while radiosurgery and nivolumab are generally safe, the combination with ipilimumab is still under study. Patients considering joining a trial should discuss possible side effects and safety with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for recurrent meningioma because they combine advanced immunotherapy with precise radiation techniques. Unlike traditional methods that mainly involve surgery and radiation alone, this approach uses nivolumab and ipilimumab, which are immune checkpoint inhibitors that help the immune system recognize and attack tumor cells more effectively. Additionally, the use of stereotactic radiosurgery allows for highly targeted radiation, potentially minimizing damage to surrounding healthy brain tissue and enhancing the overall effectiveness of treatment. By harnessing both the immune system and precision radiation, these treatments aim to offer a more powerful and targeted attack on the cancer.

What evidence suggests that this trial's treatments could be effective for recurrent meningioma?

Research has shown that stereotactic radiosurgery (SRS) can control tumor growth in patients with recurring meningioma, with success rates between 79% and 100%. In this trial, participants in Cohort A will receive Nivolumab, an immunotherapy drug that helps the immune system fight cancer cells, combined with SRS. Some studies have shown encouraging results when Nivolumab and SRS are used together. Participants in Cohort B will receive an additional treatment with Ipilimumab, another immunotherapy, which could further enhance these effects when combined with Nivolumab and SRS. This combination aims to better manage and possibly reduce tumor growth in patients with recurring grade II-III meningioma. ^{1 2 3 5 6}

Who Is on the Research Team?

Jiayi Huang

Principal Investigator

Yale University Cancer Center LAO

Are You a Good Fit for This Trial?

Adults with Grade II-III meningioma that has returned after radiation therapy can join this trial. They must have a certain level of blood cells, normal organ function, and agree to use contraception if applicable. Pregnant or breastfeeding women, those on other trials, recent chemotherapy patients, individuals with severe allergies to similar drugs or active autoimmune diseases are excluded.

Inclusion Criteria

You have enough white blood cells in your body.

ECOG performance status =< 2 (Karnofsky >= 60%)

AST/ALT =< 2.5 x institutional ULN

Exclusion Criteria

You are currently taking part in other experimental treatments.

Chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to study entry

Residual toxicities > grade 1 from prior anti-cancer therapy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive nivolumab and multi-fraction stereotactic radiosurgery, with or without ipilimumab, for up to 1 year

12 months

Regular visits every 2-4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

100 days

Follow-up visits as needed

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• Nivolumab
• Stereotactic Radiosurgery

Trial Overview The trial is testing the effectiveness and safe dosage of nivolumab combined with stereotactic radiosurgery for recurrent brain tumors (meningiomas), comparing results when used alone or alongside ipilimumab. These medications may help the immune system fight cancer by stopping tumor growth.

How Is the Trial Designed?

Group I: Cohort B (nivolumab, ipilimumab, radiosurgery) Experimental Treatment 6 Interventions

Patients receive nivolumab IV over 30 minutes every 2 weeks for 12 doses (6 months) and then every 4 weeks for additional 6 months. Patients also receive ipilimumab IV over 90 minutes on day 1. Treatment with ipilimumab repeats every 6 weeks for 4 doses in the absence of disease progression or unacceptable toxicity. Patients undergo multi-fraction stereotactic radiosurgery on days 1, 3, and 5. Patients undergo brain MRI and blood sample collection throughout the study. Patients may also undergo ECHO as clinically indicated.

Group II: Cohort A (nivolumab, radiosurgery) Experimental Treatment 5 Interventions

Patients receive nivolumab IV over 30 minutes on day 1. Cycles repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also undergo multi-fraction stereotactic radiosurgery on days 1, 3, and 5. Patients undergo brain MRI and blood sample collection throughout the study. Patients may also undergo ECHO as clinically indicated.

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+

Published Research Related to This Trial

A systematic review of 1736 patients showed that stereotactic radiotherapy (SRT) provides better radiographic tumor control and a lower risk of neurological worsening compared to stereotactic radiosurgery (SRS) in treating intracranial meningiomas.

SRS was associated with a significantly higher risk of immediate symptomatic edema and clinical neurological decline, indicating that while both treatments are safe, SRT may be the more effective option for long-term management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic radiosurgery versus stereotactic radiotherapy in the management of intracranial meningiomas: a systematic review and meta-analysis. Fatima, N., Meola, A., Pollom, EL., et al.[2020]

Gamma knife radiosurgery (GKS) was evaluated in 22 patients with malignant meningiomas, showing a 5-year survival rate of 40% and a progression-free survival rate of 26%, indicating its potential effectiveness in treating this condition.

Younger patients and those with smaller tumor sizes (less than 8 cm³) had better outcomes, suggesting that these factors are important for predicting survival and progression after GKS treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosurgery for malignant meningioma: results in 22 patients. Ojemann, SG., Sneed, PK., Larson, DA., et al.[2022]

Stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) effectively controlled aggressive Grade I and II meningiomas, with 3-year progression-free survival rates of 100% for Grade I and 83% for Grade II tumors.

However, Grade III meningiomas showed poor outcomes, with a 3-year progression-free survival rate of 0%, indicating that these malignant tumors are less responsive to SRS and SRT treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic radiation treatment for recurrent nonbenign meningiomas. Mattozo, CA., De Salles, AA., Klement, IA., et al.[2022]

In a study of 241 patients with skull base meningiomas treated with LINAC-based stereotactic radiosurgery (SRS), the long-term tumor control rate was 91.2% after a median follow-up of 102 months, indicating SRS is an effective treatment option.

The study found that previous surgery increased the risk of tumor progression, while adverse effects were linked to the maximum radiation dose to the brainstem and the tumor's location in the cerebellopontine angle.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Experience of LINAC Single-Dose Radiosurgery for Skull Base Meningiomas: A Retrospective Single-Center Study of 241 Cases. Ortiz García, IM., Rodríguez Valero, P., Jorques Infante, AM., et al.[2023]

Single-fraction radiosurgery (SRS) for intracranial meningiomas resulted in a high local control rate of 99.4% over 3 and 10 years, with most patients experiencing a decrease in tumor size and no deaths from tumor progression or radiation complications.

While SRS is effective, 12.4% of patients experienced radiation-related complications, particularly associated with larger tumor volumes and convexity/falx tumors, highlighting the importance of long-term follow-up imaging after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-fraction radiosurgery for presumed intracranial meningiomas: efficacy and complications from a 22-year experience. Pollock, BE., Stafford, SL., Link, MJ., et al.[2022]

Stereotactic radiosurgery (SRS) is a safe and effective treatment for radiation-induced meningiomas (RIMs), showing a 5-year overall survival rate of 96% and a progression-free survival rate of 68% based on a study of 29 patients with 86 lesions over a median follow-up of 59 months.

Patients with WHO grade I RIMs and those treated upfront had significantly better progression-free survival compared to those with WHO grade II RIMs or recurrent lesions, indicating that the grade and timing of treatment are crucial for outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of radiation-induced meningiomas treated with stereotactic radiosurgery. Razavian, NB., Helis, CA., Laxton, A., et al.[2023]

Stereotactic radiosurgery is an effective treatment for meningiomas, achieving tumor control rates over 85% for grade I tumors, while preserving or improving neurological function in most patients.

This technique, which uses focused radiation to target tumor cells, is increasingly being used not only for recurrent or residual meningiomas but also as an upfront treatment option, highlighting its growing importance in managing these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic radiosurgery for WHO grade I meningiomas. Sheehan, JP., Williams, BJ., Yen, CP.[2022]

This case report presents the first evidence that nivolumab, an anti-PD-1 therapy, can significantly reduce the size of a refractory meningioma in a patient being treated for advanced lung cancer.

The findings suggest that PD-1 checkpoint inhibitors may be a promising treatment avenue for meningiomas, warranting further research into their efficacy in this type of brain tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regression of intracranial meningioma following treatment with nivolumab: Case report and review of the literature. Gelerstein, E., Berger, A., Jonas-Kimchi, T., et al.[2018]

Stereotactic radiosurgery, particularly using the gamma knife technique, is highly effective for treating small intracranial meningiomas (under 3-4 cm) with excellent local control and minimal side effects.

Fractionated radiation therapy is a promising alternative for larger, inoperable meningiomas, showing encouraging results in local control and safety, although more long-term studies are needed to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fractionated radiotherapy and radiosurgery of intracranial meningiomas. Biau, J., Khalil, T., Verrelle, P., et al.[2018]

Stereotactic radiosurgery (SRS) demonstrated a high five-year tumor control probability of 92.7% for benign meningiomas, indicating it is a safe and effective treatment option for these tumors.

Fractionated stereotactic radiation therapy (FSRT) also proved to be effective, particularly for larger tumors or those near critical structures, with similar three-year tumor control rates compared to SRS, suggesting it is a viable alternative for patients who cannot undergo SRS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single dose versus fractionated stereotactic radiotherapy for meningiomas. Lo, SS., Cho, KH., Hall, WA., et al.[2022]

A study of 297 patients treated with Linac-based fractionated stereotactic radiotherapy (FSRT) for intracranial meningiomas showed high progression-free survival (PFS) rates of 92.3% at 3 years, 87% at 5 years, and 84.1% at 10 years, indicating that FSRT is an effective treatment option.

Patients who received adjuvant radiotherapy had significantly better PFS rates compared to those who underwent primary radiotherapy, and the treatment was generally safe, with less acute toxicity observed in patients receiving normofractionated radiotherapy compared to hypofractionated radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Linac-based stereotactic radiotherapy and radiosurgery in patients with meningioma. Kaul, D., Budach, V., Wurm, R., et al.[2022]

Citations

1. withpower.com withpower.com/trial/phase-2-meningioma-10-2018-bb4dd

Nivolumab + Radiosurgery for Recurrent Meningioma A systematic review of 1736 patients showed that stereotactic radiotherapy (SRT) provides better radiographic tumor control and a lower risk of neurological ...

2. mdpi.com mdpi.com/2072-6694/17/17/2750

Stereotactic Radiosurgery for Recurrent Meningioma Patients whose tumors recurred after surgery alone tended to achieve favorable outcomes with SRS, with reported favorable LC rates ranging from 79% to 100%. On ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40940847/

Stereotactic Radiosurgery for Recurrent Meningioma Results: Sixteen studies were included. For WHO Grade I tumors, 3- to 5-year progression-free survival (PFS) ranged from 85% to 100%. Grade II ...

4. researchgate.net researchgate.net/publication/394922364_Stereotactic_Radiosurgery_for_Recurrent_Meningioma_A_Systematic_Review_of_Risk_Factors_and_Management_Approaches

(PDF) Stereotactic Radiosurgery for Recurrent Meningioma Results 5 year disease-free and overall survival measured from initial SRS were 45.8% and 74.7% respectively. The 5 year lesional control rate ...

5. thejns.org thejns.org/view/journals/j-neurosurg/131/2/article-p489.xml

Outcomes and prognostic stratification of patients with ... The average survival is 6–10 months in patients with recurrent GBM (rGBM). In this study, the authors evaluated the role of stereotactic ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10477988/

Intracranial meningiomas: an update of the 2021 World Health ... Moreover, even benign meningiomas have a long-term risk of local recurrence without adjuvant radiotherapy. For low-grade tumors that are not likely to be ...