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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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.

Первичные конечные точки

• Reduction in Complement Immunosuppressive program [Срок оценки: day 0, up to 14 days]
• Reduction in Scavenger Immunosuppressive program [Срок оценки: day 0, up to 14 days]

Вторичные конечные точки (6)

• Proportion of participants needing dexamethasone within 48 hour window [Срок оценки: 48 hours]
• Safety of disulfiram [Срок оценки: 14 days]
• Change in Edema Symptom Composite Score (ESCS) [Срок оценки: day 0, up to 14 days]
• Tolerability of disulfiram [Срок оценки: 14 days]
• Change in Microglial Inflammatory program scores [Срок оценки: day 0, up to 14 days]
• Change in Systemic Inflammatory Program Scores [Срок оценки: day 0, up to 14 days]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University Hospitals Cleveland Medical Center — Cleveland

Идентификаторы

NCT: NCT07719127 · CASE7326

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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