A Study Testing the Effect of Immunotherapy (Ipilimumab and Nivolumab) in Patients With Recurrent Glioma With Elevated Mutational Burden
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ClinicalTrials.gov Identifier: NCT04145115 |
Recruitment Status :
Recruiting
First Posted : October 30, 2019
Last Update Posted : June 30, 2022
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Tracking Information | |||||||
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First Submitted Date ICMJE | October 29, 2019 | ||||||
First Posted Date ICMJE | October 30, 2019 | ||||||
Last Update Posted Date | June 30, 2022 | ||||||
Actual Study Start Date ICMJE | October 30, 2020 | ||||||
Estimated Primary Completion Date | May 31, 2023 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
Overall response rate [ Time Frame: Up to 32 months ] Assessed by the Response Assessment in Neuro-Oncology Criteria (RANO). The proportion of patients who have a confirmed tumor response will be computed as the number of patients with a confirmed complete response (CR) or confirmed partial response (PR) as determined by RANO criteria divided by the number of evaluable patients, which are eligible patients who have measurable disease and completed one cycle of treatment. Will be estimated with a binomial point estimate that will be computed as the number of responses divided by the number of evaluable patients. Exact 95% binomial confidence intervals will be generated and reported.
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Original Primary Outcome Measures ICMJE | Same as current | ||||||
Change History | |||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||
Descriptive Information | |||||||
Brief Title ICMJE | A Study Testing the Effect of Immunotherapy (Ipilimumab and Nivolumab) in Patients With Recurrent Glioma With Elevated Mutational Burden | ||||||
Official Title ICMJE | A Phase II Study of Checkpoint Blockade Immunotherapy in Patients With Somatically Hypermutated Recurrent WHO Grade 4 Glioma | ||||||
Brief Summary | This phase II trial studies the effect of immunotherapy drugs (ipilimumab and nivolumab) in treating patients with glioma that has come back (recurrent) and carries a high number of mutations (mutational burden). Cancer is caused by changes (mutations) to genes that control the way cells function. Tumors with high number of mutations may respond well to immunotherapy. Immunotherapy with monoclonal antibodies such as ipilimumab and nivolumab may help the body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Giving ipilimumab and nivolumab may lower the chance of recurrent glioblastoma with high number of mutations from growing or spreading compared to usual care (surgery or chemotherapy). | ||||||
Detailed Description | PRIMARY OBJECTIVE: I. To determine whether the combination of ipilimumab and nivolumab increases the tumor response rate assessed by modified Response Assessment in Neuro-Oncology (RANO) Criteria in patients with hypermutated recurrent glioblastoma. SECONDARY OBJECTIVES: I. Estimate the overall survival distribution, median survival, and one-year survival rate of patients with hypermutated, recurrent glioblastoma who are treated with ipilimumab and nivolumab. II. Estimate the progression-free survival distribution and median progression-free survival of patients with hypermutated, recurrent glioblastoma who are treated with ipilimumab and nivolumab. III. Determine the adverse event profile of patients with hypermutated, recurrent glioblastoma who are treated with ipilimumab and nivolumab. EXPLORATORY OBJECTIVES: I. Test whether PD-L1 or immunologic infiltrate in the tumor microenvironment are associated with objective tumor response, overall survival, progression-free survival, tumor mutational burden, or rates of grade 3 or higher adverse events. II. Test whether MGMT status, microsatellite instability (MSI) status, mutational signatures, or amount of tumor mutational burden (TMB) including germline analysis are associated with objective tumor response, overall survival, progression-free survival, or rates of grade 3 or higher adverse events. III. Evaluate associations between exome and transcriptome gene levels with objective tumor response, overall survival, progression-free survival, rates of grade 3 or higher adverse events. IV. Evaluate associations between the gut microbiome and objective tumor response. V. Response rate using immunotherapy (i)RANO. OUTLINE: Patients receive nivolumab intravenously (IV) over 30 minutes and ipilimumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 30 minutes on day 1. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients without disease progression are followed every 8 weeks until disease progression, then every 3 months for up to 3 years. Patients with disease progression after completion of study treatment are followed every 3 months for up to 3 years. |
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Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 2 | ||||||
Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE | Experimental: Treatment (nivolumab, ipilimumab)
Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 30 minutes on day 1. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Interventions:
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Publications * | Not Provided | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||
Recruitment Status ICMJE | Recruiting | ||||||
Estimated Enrollment ICMJE |
37 | ||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||
Estimated Study Completion Date ICMJE | May 31, 2023 | ||||||
Estimated Primary Completion Date | May 31, 2023 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE | Inclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||
Accepts Healthy Volunteers ICMJE | No | ||||||
Contacts ICMJE | |||||||
Listed Location Countries ICMJE | Puerto Rico, United States | ||||||
Removed Location Countries | |||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT04145115 | ||||||
Other Study ID Numbers ICMJE | NCI-2019-07242 NCI-2019-07242 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) A071702 ( Other Identifier: Alliance for Clinical Trials in Oncology ) A071702 ( Other Identifier: CTEP ) U10CA180821 ( U.S. NIH Grant/Contract ) |
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Has Data Monitoring Committee | No | ||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Current Responsible Party | National Cancer Institute (NCI) | ||||||
Original Responsible Party | Same as current | ||||||
Current Study Sponsor ICMJE | National Cancer Institute (NCI) | ||||||
Original Study Sponsor ICMJE | Same as current | ||||||
Collaborators ICMJE | Not Provided | ||||||
Investigators ICMJE |
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PRS Account | National Cancer Institute (NCI) | ||||||
Verification Date | June 2022 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |