Nivolumab + Radiosurgery for Recurrent Meningioma

Recruiting at 29 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

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

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial studies how well nivolumab and stereotactic radiosurgery, with or without ipilimumab, work in treating patients whose grade II-III meningioma has returned. The treatment aims to boost the immune system to fight cancer and use precise radiation to shrink the tumor. Nivolumab and ipilimumab are immune checkpoint inhibitors that have shown promise in treating various cancers, including brain metastases from melanoma.

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.

What data supports the effectiveness of the treatment Nivolumab + Radiosurgery for Recurrent Meningioma?

Research shows that stereotactic radiosurgery (a type of precise radiation treatment) is effective in controlling tumor growth in meningiomas, with tumor control rates over 85% for certain types. Additionally, stereotactic radiotherapy (a similar treatment) has been found to offer better tumor control and fewer side effects compared to stereotactic radiosurgery. ^{1 2 3 4 5}

Is the combination of Nivolumab and radiosurgery safe for treating recurrent meningioma?

Stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) are generally safe for treating intracranial meningiomas, but SRS may lead to a higher risk of neurological issues and swelling compared to SRT. Further studies are needed to confirm these findings. ^{1 5 6 7 8}

How does the treatment of Nivolumab + Radiosurgery for Recurrent Meningioma differ from other treatments?

This treatment is unique because it combines nivolumab, an immune checkpoint inhibitor that targets PD-1 to help the immune system attack cancer cells, with stereotactic radiosurgery (SRS), a precise form of radiation therapy. This combination aims to enhance the effectiveness of treatment for recurrent meningioma, a condition with limited standard treatment options. ^{1 5 9 10 11}

Research Team

Jiayi Huang

Principal Investigator

Yale University Cancer Center LAO

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• Ipilimumab (Checkpoint Inhibitor)
• Nivolumab (Checkpoint Inhibitor)
• Stereotactic Radiosurgery (Radiation)

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.

Participant Groups

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.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

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]

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]

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]

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]

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 (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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Stereotactic radiosurgery versus stereotactic radiotherapy in the management of intracranial meningiomas: a systematic review and meta-analysis. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Stereotactic radiation treatment for recurrent nonbenign meningiomas. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Linac-based stereotactic radiotherapy and radiosurgery in patients with meningioma. [2022]

4. United States 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. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Stereotactic radiosurgery for WHO grade I meningiomas. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Single-fraction radiosurgery for presumed intracranial meningiomas: efficacy and complications from a 22-year experience. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Outcomes of radiation-induced meningiomas treated with stereotactic radiosurgery. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Single dose versus fractionated stereotactic radiotherapy for meningiomas. [2022]

9. France pubmed.ncbi.nlm.nih.gov

Fractionated radiotherapy and radiosurgery of intracranial meningiomas. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Radiosurgery for malignant meningioma: results in 22 patients. [2022]

11. Scotland pubmed.ncbi.nlm.nih.gov

Regression of intracranial meningioma following treatment with nivolumab: Case report and review of the literature. [2018]