Immunotherapy meets radiation in fight against recurrent meningioma
NCT ID NCT03604978
First seen Jun 27, 2026 · Last updated Jul 31, 2026 · Updated 1 time
Summary
This study is for people with a rare, aggressive brain tumor called high-grade meningioma that has come back after radiation. It tests whether adding immunotherapy drugs (nivolumab with or without ipilimumab) to precise, high-dose radiation can help shrink the tumor or slow its growth. The goal is to find the safest dose and see how well the combination works. About 38 adults will take part.
This is an AI summary of the original study and may miss details. Read our disclaimer.
Study facts
What this study's own registry entry says, in plain language.
- Phase
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Phase 1/2
Runs two stages together: safety and dose first, then whether the treatment works.
- Participants
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About 38 people
The number the study aims to enrol. It can still change while the study runs.
- Started
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Jun 2019
- Expected to finish
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Mar 2027
An estimate. End dates often move.
- Lead sponsor
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A government research agency
The lead sponsor is the US National Institutes of Health.
Who can take part
This study's own entry requirements. Only the study team can say for certain whether you qualify.
- Ages
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18 years and older
- Sex
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Anyone
- Healthy volunteers
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Not accepted
This study is not open to healthy volunteers. The entry requirements below say who it is open to.
Show the full entry requirements Hide the full entry requirements
Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.
Inclusion Criteria: * Patients must have histologically confirmed World Health Organization (WHO) grade II-III meningioma which has relapsed after prior radiation therapy with radiologically progressive or recurrent disease * Patients must have measurable disease, defined as at least 1 lesion that can be accurately measured in at least one dimension as \>= 1 cm on brain magnetic resonance imaging (MRI) but with the maximum dimension =\< 5 cm OR gross tumor volume \< 20 cm\^3. All the relapsed disease would need to be eligible to be treated with reirradiation * Patients must have at least one prior surgery with available archival formalin-fixed paraffin-embedded (FFPE) tumor blocks of the initial or recurrent meningioma. If there are multiple tumor blocks from multiple surgeries, the most recent tumor block (and ideally of the relapsed tumor after initial radiation therapy) should be submitted. If a tumor block is not available, an alternative of 20-30 unstained slides may be submitted instead. Annotation regarding whether the tumor block is before or after initial radiation therapy should be provided * Prior initial radiation therapy may include external beam radiation or radiosurgery, or combination of both. However, the total dose of prior radiation exposure to the site of recurrent tumor (for consideration of re-irradiation) cannot be more than 70 Gy. The duration since the previous radiation exposure to the site of reirradiation need to be at least 6 months * Age \>= 18 years * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%) * Leukocytes \>= 3,000/mcL * Absolute neutrophil count \>= 1,500/mcL * Platelets \>= 100,000/mcL * Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN * Serum creatinine =\< 1.5 x institutional ULN OR glomerular filtration rate (GFR) \>= 30 mL/min/1.73 m\^2 for patients with creatinine levels above 1.5 x institutional normal * The effects of nivolumab and/or ipilimumab on the developing human fetus are unknown. For this reason and because radiation therapy is known to be teratogenic, women of childbearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. WOCBP should use an adequate method to avoid pregnancy for 5 months after the last dose of investigational drug. Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 24 hours prior to the start of nivolumab. Women must not be breastfeeding. Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile as well as azoospermic men) do not require contraception * Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL * WOCBP receiving nivolumab will be instructed to adhere to contraception for a period of 5 months after the last dose of investigational product. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product. These durations have been calculated using the upper limit of the half-life for nivolumab (25 days) and are based on the protocol requirement that WOCBP use contraception for 5 half-lives plus 30 days and men who are sexually active with WOCBP use contraception for 5 half-lives plus 100 days * Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately * Ability to understand and the willingness to sign a written informed consent document or, if decision-making capacity is impaired, consent of a legally authorized representative (e.g., spouse, adult child, live-in caretaker). Exclusion Criteria: * Patients who have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study * Patients who have had radiation therapy (to the site of reirradiation) within 6 months prior to entering the study * Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1); however, alopecia, sensory neuropathy =\< grade 2, or other =\< grade 2 not constituting a safety risk based on the investigator's judgment are acceptable * Patients who are receiving any other investigational agents * Patients who have previous treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways * History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab and/or ipilimumab * History of severe hypersensitivity reaction to any monoclonal antibody * Current use of immunosuppressive medication (EXCEPT for the following: Intranasal, inhaled, topical steroids, or local steroid injection \[e.g. intra-articular injection\]; systemic corticosteroids at doses =\< 4 mg/day of dexamethasone or equivalent; steroids as premedication for hypersensitivity reactions \[e.g. computed tomography (CT) scan premedication\]) * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. However, patients with human immunodeficiency virus (HIV) on stable therapy with minimal viral loads and patients with hepatitis B and hepatitis C who have received treatment with minimal viral loads will be eligible * Pregnant women are excluded from this study because radiation therapy is teratogenic and that the effects of nivolumab and/or ipilimumab on the developing human fetus are unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with nivolumab and/or ipilimumab, breastfeeding should be discontinued if the mother is treated with nivolumab and/or ipilimumab * Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, should be excluded. These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease. Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible. Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible * Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event) * Prior organ transplantation including allogeneic stem cell transplantation * Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis, or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior, or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study * Live vaccination within 4 weeks of the first dose of nivolumab and while on trial is prohibited except for administration of inactivated vaccines
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Conditions
The condition(s) this trial relates to.
As listed by the trial registrant
The condition terms exactly as the trial's registrant entered them.
Contacts and locations
Locations
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City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
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Duke University Medical Center
Durham, North Carolina, 27710, United States
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Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
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Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
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Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
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Los Angeles General Medical Center
Los Angeles, California, 90033, United States
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Mayo Clinic Hospital in Arizona
Phoenix, Arizona, 85054, United States
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Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980, United States
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Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
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NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
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Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141, United States
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Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107, United States
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UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
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UC San Diego Moores Cancer Center
La Jolla, California, 92093, United States
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UCHealth University of Colorado Hospital
Aurora, Colorado, 80045, United States
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UM Sylvester Comprehensive Cancer Center at Aventura
Aventura, Florida, 33180, United States
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UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146, United States
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UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442, United States
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UM Sylvester Comprehensive Cancer Center at Kendall
Miami, Florida, 33176, United States
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UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, 33324, United States
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UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
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UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232, United States
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USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
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UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
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University of Kansas Cancer Center
Kansas City, Kansas, 66160, United States
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University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205, United States
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University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
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University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
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Washington University School of Medicine
St Louis, Missouri, 63110, United States
More trials for these conditions
Other studies related to the condition(s) this trial covers.
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- Can molecular markers decide who needs radiation after meningioma surgery?
- New radiation approach aims to stop brain tumor regrowth
- New combo therapy aims to stop returning brain tumors
- New radiation strategy aims to tackle tough brain tumors
- New hope for inoperable brain tumors: radioactive drug trial launches