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.
PRIMARY OBJECTIVES: I. 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: I. 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: I. 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
38
Undergo blood sample collection
Undergo ECHO
Given IV
Undergo brain MRI
Given IV
Undergo multi-fraction stereotactic radiosurgery
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, United States
City of Hope Comprehensive Cancer Center
Duarte, California, United States
UC San Diego Moores Cancer Center
La Jolla, California, United States
Los Angeles General Medical Center
Los Angeles, California, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
Maximum tolerated combination of radiosurgery and nivolumab plus or minus ipilimumab (Phase I)
Time frame: Up to 100 days
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).
Time frame: Up to 100 days
Objective response rate (Phase II)
Time frame: From the start of treatment through at least two years of follow-up
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.
Time frame: Up to 100 days
Progression-free survival
80% confidence intervals will be assessed using Kaplan-Meier product limit methods.
Time frame: From the start of treatment to 6 months and 2 years
Overall survival
80% confidence intervals will be assessed using Kaplan-Meier product limit methods.
Time frame: From the start of treatment through at least two years of follow-up
Duration of overall response
Time frame: From the start of treatment through at least two years of follow-up
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UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, United States
UCHealth University of Colorado Hospital
Aurora, Colorado, United States
UM Sylvester Comprehensive Cancer Center at Aventura
Aventura, Florida, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, United States
...and 19 more locations