Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Glioma

Glioblastoma

Astrocytoma

Neoplasm Metastasis

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Antibodies

Antibodies, Monoclonal

Immunomodulating Agents

Ipilimumab

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

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. Patients also undergo MRI throughout the study.

Magnetic Resonance Imaging

Gavin P Dunn

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).

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. Patients also undergo magnetic resonance imaging (MRI) throughout the study.

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.

A Study Testing the Effect of Immunotherapy (Ipilimumab and Nivolumab) in Patients With Recurrent Glioma With Elevated Mutational Burden

A Phase II Study of Checkpoint Blockade Immunotherapy in Patients With Somatically Hypermutated Recurrent WHO Grade 4 Glioma

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

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.

Will be summarized using Kaplan-Meier (KM) estimators. Survival curves will be generated from the KM estimators. KM estimates will be determined for the median OS as well as the 12-month OS rates. Confidence intervals will be provided for the median values as well as the one-year rates.

Will be summarized using KM estimators. Survival curves will be generated from the KM estimators. KM estimates will be determined for the median PFS as well as the 12-month PFS rates. Confidence intervals will be provided for the median values as well as the one-year rates.

The AEs will be summarized by the frequency and relative frequency of the maximum grade experienced by the patients for all recorded AEs. Adverse event data will be summarized by each observed AE with the number of patients who reported the AE as well as the proportion of patients with the AE.

National Cancer Institute (NCI)

Spots Global Cancer Trial Database for secondary glioblastoma