A Window-of-Opportunity Study of Disulfiram to Reduce Myeloid Immunosuppression and Steroid Dependence in Resectable High-Grade Glioma
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Reduction in Complement Immunosuppressive program
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
Reduction in Complement Immunosuppressive program
时间窗: day 0, up to 14 days
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.
Reduction in Scavenger Immunosuppressive program
时间窗: day 0, up to 14 days
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.
次要结局
- Proportion of participants needing dexamethasone within 48 hour window(48 hours)
- Safety of disulfiram(14 days)
- Change in Edema Symptom Composite Score (ESCS)(day 0, up to 14 days)
- Tolerability of disulfiram(14 days)
- Change in Microglial Inflammatory program scores(day 0, up to 14 days)
- Change in Systemic Inflammatory Program Scores(day 0, up to 14 days)