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Grade 2 MeningiomaPhase 1/2NCT03604978

Nivolumab and Multi-fraction Stereotactic Radiosurgery With or Without Ipilimumab in Treating Patients With Recurrent Grade II-III Meningioma

A Phase 1/2 study testing Biospecimen Collection, Echocardiography Test and Ipilimumab in people with Grade 2 Meningioma and Grade 3 Meningioma, run by National Cancer Institute (NCI) at 29 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This phase I/II trial studies the side effects and best dose of nivolumab when given together with multi-fraction stereotactic radiosurgery and to see how well they work with or without ipilimumab in treating patients with grade II-III meningioma that has come back (recurrent). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biospecimen Collection, Echocardiography Test and Ipilimumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
38 participants
Where
29 sitesUnited States
Study dates
17 Jun 2019to 19 Mar 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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%)
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  • 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).

Who cannot join

  • 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
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  • 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

Trial locations and contacts

29 sites in 1 country.

29 sites in 1 country

United States29 sites

  • UCHealth University of Colorado Hospital

    Aurora, Colorado, 80045

  • UM Sylvester Comprehensive Cancer Center at Aventura

    Aventura, Florida, 33180

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • UM Sylvester Comprehensive Cancer Center at Coral Gables

    Coral Gables, Florida, 33146

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • UM Sylvester Comprehensive Cancer Center at Deerfield Beach

    Deerfield Beach, Florida, 33442

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

  • UC San Diego Moores Cancer Center

    La Jolla, California, 92093

  • Los Angeles General Medical Center

    Los Angeles, California, 90033

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • UM Sylvester Comprehensive Cancer Center at Kendall

    Miami, Florida, 33176

  • Laura and Isaac Perlmutter Cancer Center at NYU Langone

    New York, New York, 10016

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • UC Irvine Health/Chao Family Comprehensive Cancer Center

    Orange, California, 92868

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • Mayo Clinic Hospital in Arizona

    Phoenix, Arizona, 85054

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • UM Sylvester Comprehensive Cancer Center at Plantation

    Plantation, Florida, 33324

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • University of Kansas Hospital-Westwood Cancer Center

    Westwood, Kansas, 66205

Other trials in United States

About this study

Official title: A Phase I/II Study of Nivolumab Plus or Minus Ipilimumab in Combination With Multi-Fraction Stereotactic Radiosurgery for Recurrent High-Grade Radiation-Relapsed Meningioma

This phase I/II trial studies the side effects and best dose of nivolumab when given together with multi-fraction stereotactic radiosurgery and to see how well they work with or without ipilimumab in treating patients with grade II-III meningioma that has come back (recurrent). Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may cause less damage to normal tissue. Giving nivolumab and multi-fraction stereotactic radiosurgery with or without ipilimumab may work better in treating patients with grade II-III meningioma.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the maximum tolerated combination and safety profile of multi-fraction radiosurgery with concurrent nivolumab plus or minus ipilimumab for recurrent radiation-relapsed high-grade meningioma. (Phase I) II. To evaluate the objective response rate (ORR), either complete response or partial response as assessed on magnetic resonance imaging (MRI) per the modified Macdonald Criteria, of multi-fraction radiosurgery with concurrent nivolumab plus or minus ipilimumab for recurrent radiation-relapsed high-grade meningioma. (Phase II)

SECONDARY OBJECTIVE:

  1. To evaluate duration of overall response, progression-free survival (PFS) and overall survival (OS) of recurrent radiation-relapsed high-grade meningioma patients treated with the combination of multi-fraction radiosurgery and nivolumab plus or minus ipilimumab.

CORRELATIVE OBJECTIVES:

  1. To analyze the immunophenotype changes of peripheral T-cells during the treatment with multi-fraction radiosurgery in combination with nivolumab plus or minus ipilimumab.

II. To perform molecular profiling assays on pretreatment/baseline archival tumor, including, but not limited to, whole exome sequencing (WES) and messenger ribonucleic acid (RNA) sequencing (RNAseq), in order to IIa. Identify potential predictive and prognostic biomarkers (such as neoantigen signature or mutation burden) beyond any genomic alteration by which treatment may be assigned.

IIb. Identify resistance mechanisms using genomic deoxyribonucleic acid (DNA)- and RNA-based assessment platforms.

III. To contribute genetic analysis data from de-identified biospecimens to Genomic Data Commons (GDC), a well annotated cancer molecular and clinical data repository, for current and future research; specimens will be annotated with key clinical data, including presentation, diagnosis, staging, summary treatment, and if possible, outcome.

IV. To bank formalin-fixed, paraffin-embedded (FFPE) tissue, blood (for cell-free DNA analysis), and nucleic acids obtained from patients at the National Cancer Institute Early-Phase and Experimental Clinical Trials Biospecimen Bank (EET Biobank).

OUTLINE: This is a phase I, dose-escalation study of nivolumab followed by a phase II study. Patients are randomized to 1 of 2 cohorts.

COHORT A: Patients receive nivolumab intravenously (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.

COHORT B: 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 echocardiography (ECHO) as clinically indicated.

After completion of study treatment, patients are followed up for 100 days.

Being tested
Biospecimen Collection, Echocardiography Test, Ipilimumab, Magnetic Resonance Imaging, Nivolumab
Medical subject headings
Meningioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo blood sample collection

  • Echocardiography TestProcedure or surgery

    Also called EC, Echocardiography

    Undergo ECHO

  • IpilimumabBiological

    Also called Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS 734016, BMS-734016, BMS734016

    Given IV

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo brain MRI

  • NivolumabBiological

    Also called ABP 206, BCD-263, BMS 936558, BMS-936558

    Given IV

  • Stereotactic RadiosurgeryRadiation

    Also called SRS, Stereotactic External Beam Irradiation, stereotactic external-beam radiation therapy, Stereotactic Radiation Therapy

    Undergo multi-fraction stereotactic radiosurgery

Study groups in NCT03604978
Study groupRoleWhat they receive
Cohort A (nivolumab, radiosurgery)ExperimentalPatients 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.
Receives: Procedure: Biospecimen Collection; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Biological: Nivolumab; Radiation: Stereotactic Radiosurgery
Cohort B (nivolumab, ipilimumab, radiosurgery)ExperimentalPatients 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.
Receives: Procedure: Biospecimen Collection; Procedure: Echocardiography Test; Biological: Ipilimumab; Procedure: Magnetic Resonance Imaging; Biological: Nivolumab; Radiation: Stereotactic Radiosurgery

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum tolerated combination of radiosurgery and nivolumab plus or minus ipilimumab (Phase I)

    Measured: Up to 100 days

  2. Incidence of adverse event profile (Phase I)

    Will be evaluated by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The number and percentage of subjects experiencing each type of adverse event will be tabulated by severity, and relationship to treatment. If appropriate, confidence intervals will be used to characterize the precision of the estimate. A complete listing of adverse events will also be tabulated, and will provide details including severity, relationship to treatment, onset, duration, and outcome. Laboratory data measured on a continuous scale will be characterized by summary statistics (mean and standard deviation).

    Measured: Up to 100 days

  3. Objective response rate (Phase II)

    Measured: From the start of treatment through at least two years of follow-up

  4. Objective radiological response (Phase II)

    Will include either complete response or partial response as assessed on magnetic resonance imaging per the modified Macdonald Criteria. 80% confidence intervals will be calculated.

    Measured: Up to 100 days

Secondary outcomes (3)

  1. Progression-free survival

    80% confidence intervals will be assessed using Kaplan-Meier product limit methods.

    Measured: From the start of treatment to 6 months and 2 years

  2. Overall survival

    80% confidence intervals will be assessed using Kaplan-Meier product limit methods.

    Measured: From the start of treatment through at least two years of follow-up

  3. Duration of overall response

    Measured: From the start of treatment through at least two years of follow-up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jul 2018
  2. Study start17 Jun 2019
  3. Primary completion19 Mar 2027 (estimated)
  4. Study completion19 Mar 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
38 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03604978
Sponsor's protocol ID
NCI-2018-01560
Other IDs
NCI-2018-01560, 201901009, 10186, 10186, UM1CA186689, UM1CA186704
Status last verified
Jul 2026
First submitted
27 Jul 2018
Last updated
31 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Biospecimen Collection, Echocardiography Test and Ipilimumab in people with Grade 2 Meningioma and Grade 3 Meningioma, run by National Cancer Institute (NCI) at 29 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 31 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 29 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated combination of radiosurgery and nivolumab plus or minus ipilimumab (Phase I) (time frame: Up to 100 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03604978.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2026.

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