This research study is for participants with glioblastoma. It can cause a tumor immunosuppression which helps myeloid cells that can stop T-cell function. Disulfiram is a drug that has been used in treating other disorders, but this study will examine if disulfiram can help make the tumor environment less immunosuppressive and reduce brain swelling when taken before surgery.
Glioblastoma is one of the most common brain cancers that affect adults and is very hard to treat. This is due to myeloid cells, which are special immune cells in the body that prevent the body from recognizing and attacking the tumor. Because of this, immunotherapies have not worked well in treating glioblastoma. Disulfiram may also reduce brain swelling, which may decrease or delay the need for subjects to be treated with steroids. The purpose of this study is to find out if disulfiram can help reduce immunosuppression and help prevent edema symptoms when taken 3-14 days before planned surgery.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
20
250 milligrams (mg) disulfiram will be given daily for 3-14 prior to operation. Participants can have the option to be treated at 500mg after initial evaluation.
University Hospitals Cleveland Medical Center
Cleveland, Ohio, United States
Reduction in Complement Immunosuppressive program
Evaluate whether disulfiram given pre-operation reduces the Complement Immunosuppressive myeloid program scores vs historical controls, which will be compared using a two-sample Wilcoxon rank-sum test (primary) and a two-sample t-test on the participant-level program scores (sensitivity). Measured using scRNA-sequence data.
Time frame: day 0, up to 14 days
Reduction in Scavenger Immunosuppressive program
Evaluate whether disulfiram given pre-operation reduces the Scavenger Immunosuppressive myeloid program scores vs historical controls, which will be compared using a two-sample Wilcoxon rank-sum test (primary) and a two-sample t-test on the participant-level program scores (sensitivity). Measured using scRNA-sequence data.
Time frame: day 0, up to 14 days
Proportion of participants needing dexamethasone within 48 hour window
Change in investigator-rated edema symptom composite score from baseline to Day 2 on therapy.
Time frame: 48 hours
Safety of disulfiram
Safety is defined as the rates of adverse events experienced by participants. Adverse event severity is graded according to the NCI Common Terminology for Adverse Events (CTCAE) Version 5.0
Time frame: 14 days
Change in Edema Symptom Composite Score (ESCS)
Change in ESCS is analyzed using a Wilcoxon signed-rank test
Time frame: day 0, up to 14 days
Tolerability of disulfiram
Tolerability as measured by participant toxicity rates.
Time frame: 14 days
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Change in Microglial Inflammatory program scores
Evaluate the change in microglial inflammatory program scores vs historical controls, which will be compared using a two-sample Wilcoxon rank-sum test (primary) and a two-sample t-test on the participant-level program scores (sensitivity). Measured using scRNA-sequence data.
Time frame: day 0, up to 14 days
Change in Systemic Inflammatory Program Scores
Evaluate the change in systemic inflammatory program scores vs historical controls, which will be compared using a two-sample Wilcoxon rank-sum test (primary) and a two-sample t-test on the participant-level program scores (sensitivity). Measured using scRNA-sequence data.
Time frame: day 0, up to 14 days