Study of Disulfiram to Reduce Myeloid Immunosuppression and Steroid Dependence in Resectable High Grade Glioma

A Window-of-Opportunity Study of Disulfiram to Reduce Myeloid Immunosuppression and Steroid Dependence in Resectable High-Grade Glioma

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Brain (Nervous System) Cancers
• Intervention / Treatment: Drug: Disulfiram (DSF)

Detailed Description

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
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Tiffany Hodges, MD; Phone Number: 216-286-7122; Email: tiffany.hodges@uhhospitals.org

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
      • Contact: Tiffany Hodges, MD; Phone Number: 216-286-7122; Email: tiffany.hodges@uhhospitals.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years.
• Radiographically suspected or confirmed high-grade glioma planned for surgical resection as part of standard clinical care.
• Able to start disulfiram at least 3 days prior to planned surgery (treatment window 3-14 days pre-op).
• In-patient status for the duration of study.
• Karnofsky Performance Status (KPS) ≥70%.

• Adequate organ function within 14 days prior to first dose:

  • ANC ≥1.5 x 10^9/L
  • Platelets ≥100 x 10^9/L
  • Hemoglobin ≥9 g/dL
  • AST/ALT ≤2.5 x ULN
  • Total bilirubin ≤1.5 x ULN (unless Gilbert syndrome, in which case <5 x ULN).
• Total bilirubin ≤1.5 x ULN (unless Gilbert syndrome, in which case <5 x ULN).
• Ability to understand and willingness to sign written informed consent.
• Willingness to avoid alcohol and alcohol-containing products during treatment and for 14 days after last dose.

Exclusion Criteria:

• Any dexamethasone (or other systemic glucocorticoid for cerebral edema) administered prior to enrollment/first dose (including outpatient or ED administration). This does not include inhalers or topical steroids.
• Imaging features that are atypical for high-grade glioma that have reasonable concern for competing differential diagnoses (e.g. PCNSL, tumefactive MS, etc.)
• Known hypersensitivity to disulfiram or thiuram derivatives.
• Active or severe hepatic disease (e.g. hepatitis, cirrhosis, known liver disease that may be exacerbated by disulfiram), or baseline liver tests above inclusion thresholds.
• Current use of metronidazole or other contraindicated interacting medications. See section 6.0; medication reconciliation for the list of medications/foods.
• Pregnant or breastfeeding. Pregnant women are excluded from the trial because the safety in pregnancy has not been established. Women who are breastfeeding are excluded from the trial because it is not known if disulfiram is present in breast milk.
• Clinically unstable neurologic status requiring immediate steroid initiation, where delaying dexamethasone for a disulfiram trial would be unsafe (investigator judgment).
• Any condition that would limit compliance with alcohol avoidance or study procedures, or that would make participation unsafe in investigator judgment.
• Subjects receiving any other investigational agents.
• Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled or unstable cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Disulfiram; description here	Drug: Disulfiram (DSF); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	day 0, up to 14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants needing dexamethasone within 48 hour window	Change in investigator-rated edema symptom composite score from baseline to Day 2 on therapy.	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	14 days
Change in Edema Symptom Composite Score (ESCS)	Change in ESCS is analyzed using a Wilcoxon signed-rank test	day 0, up to 14 days
Tolerability of disulfiram	Tolerability as measured by participant toxicity rates.	14 days
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.	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.	day 0, up to 14 days

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Investigators: Principal Investigator: Tiffany Hodges, MD, University Hospitals Cleveland Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): December 17, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: July 17, 2026
• First Submitted That Met QC Criteria: July 17, 2026
• First Posted (Actual): July 22, 2026

Study Record Updates

• Last Update Posted (Actual): July 22, 2026
• Last Update Submitted That Met QC Criteria: July 17, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: brain and nervous system
• Additional Relevant MeSH Terms: Nervous System Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Neoplasms; Neurologic Manifestations; Sulfur Compounds; Organic Chemicals; Acids, Acyclic; Carboxylic Acids; Sulfides; Carbamates; Ditiocarb; Thiocarbamates; Disulfides; Disulfiram
• Other Study ID Numbers: CASE7326

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data that underlie published results will be shared, as permitted by the informed consent, IRB approval, and institutional policy. This may include data dictionaries and de-identified clinical data elements needed to reproduce reported analyses, including eligibility and baseline characteristics, disulfiram exposure, dexamethasone/steroid exposure, edema-related symptom assessments, safety/adverse event data, and correlative assay-derived results from blood, tumor tissue, and CSF. Individual-level molecular, single-cell, spatial, or sequencing data will be shared only in de-identified and/or controlled-access form, as appropriate.
• IPD Sharing Time Frame: Data supporting published results will be made available beginning after publication of the primary results and completion of institutional review for data release. Data will remain available for at least 3 years after publication, or longer if required by repository, journal, sponsor, or institutional policy.
• IPD Sharing Access Criteria: Access will be provided to qualified investigators for scientifically and ethically appropriate research uses, after review and approval of a written request, execution of any required data use agreement, and confirmation that the proposed use is consistent with the informed consent, IRB approval, and institutional policies. Controlled-access data will not include direct identifiers.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes