This phase I trial studies the safety and best dose of ipilimumab, nivolumab, or both in combination with temozolomide in treating patients with newly diagnosed glioblastoma or gliosarcoma. Monoclonal antibodies, such as ipilimumab and nivolumab, may block tumor growth in different ways by targeting certain cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known which combination is a better treatment for glioblastoma or gliosarcoma.
PRIMARY OBJECTIVES: I. Determine the maximum safe dose of single-agent treatment with ipilimumab, nivolumab and the combination when given with temozolomide during maintenance treatment for newly diagnosed glioblastoma. SECONDARY OBJECTIVES: I. Collect and record the side effect profiles for single-agent treatment with ipilimumab, nivolumab, and the combination when given with temozolomide during the maintenance phase for newly diagnosed glioblastoma. II. Perform pilot studies of immune cells within tumor samples, e.g. phenotyping tumor infiltrating lymphocytes (TILs) by interrogating tumor tissues from diagnostic tumor blocks. III. Report the number of patients alive at 1 and 2 years after the start of single-agent treatment with ipilimumab, nivolumab, and the combination when given with temozolomide during the maintenance phase for newly diagnosed glioblastoma. OUTLINE: Patients are randomized to 1 of 3 treatment arms. ARM I: Within 5 weeks after completion of chemoradiation, patients receive temozolomide orally (PO) on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive ipilimumab intravenously (IV) over 90 minutes once every 4 weeks for 4 courses and then beginning 3 months after course 4 once every 3 months for 4 courses in the absence unacceptable toxicity. ARM II: Within 5 weeks after completion of chemoradiation, patients receive temozolomide PO on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive nivolumab IV over 60 minutes once every 2 weeks for 16 weeks and then once every 2 weeks for 48 weeks in the absence unacceptable toxicity. ARM III: Within 5 weeks after completion of chemoradiation, patients receive temozolomide PO on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive ipilimumab IV over 90 minutes once every 4 weeks for 4 courses and nivolumab IV over 60 minutes once every 2 weeks for 64 weeks in the absence unacceptable toxicity. After completion of study treatment, patients are followed up at 1 month, and then every 3 months for 1 year, every 4 months for 1 year, and then every 6 months thereafter.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
32
UCSF Medical Center-Parnassus
San Francisco, California, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, United States
National Institutes of Health Clinical Center
Bethesda, Maryland, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, United States
Case Western Reserve University
Cleveland, Ohio, United States
Cleveland Clinic Cancer Center/Fairview Hospital
Cleveland, Ohio, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
...and 1 more locations
Immune-related dose-limiting toxicities for the single-agent treatment with ipilimumab
The frequency and severity of toxicities will be reported.
Time frame: Up to 8 weeks
Immune-related dose-limiting toxicities for the single-agent treatment with nivolumab
The frequency and severity of toxicities will be reported.
Time frame: Up to 8 weeks
Immune-related dose-limiting toxicities for the combination of ipilimumab and nivolumab when given with temozolomide
The frequency and severity of toxicities will be reported.
Time frame: Up to 8 weeks
Incidence of adverse events, graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Will collect and record the side effect profiles for single-agent treatment with ipilimumab, nivolumab, and the combination when given with temozolomide during the maintenance phase for newly diagnosed glioblastoma.
Time frame: Up to 1 month post-treatment
Biomarker analysis of immune cells within tumor samples using standard immunohistochemistry
The results of this battery of assays will be used to obtain pilot data and an assessment of feasibility in obtaining reproducible results in preparation for a subsequent randomized, statistically powered comparative clinical trial.
Time frame: Up to 1 month post-treatment
Number of patients who are alive
The number of patients who are alive at 1 year will be reported.
Time frame: 1 year after the start of immunotherapy treatment
Number of patients who are alive
The number of patients who are alive at 2 years will be reported.
Time frame: 2 years after the start of immunotherapy treatment
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