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.
Tutkimuksen yleiskatsaus
Tila
Interventio / Hoito
Yksityiskohtainen kuvaus
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.
Opintotyyppi
Ilmoittautuminen (Arvioitu)
Vaihe
- Vaihe 1
Yhteystiedot ja paikat
Opiskeluyhteys
- Nimi: Tiffany Hodges, MD
- Puhelinnumero: 216-286-7122
- Sähköposti: tiffany.hodges@uhhospitals.org
Opiskelupaikat
-
-
Ohio
-
Cleveland, Ohio, Yhdysvallat, 44106
- University Hospitals Cleveland Medical Center
-
-
Osallistumiskriteerit
Kelpoisuusvaatimukset
Opintokelpoiset iät
Hyväksyy terveitä vapaaehtoisia
Sukupuolet, jotka voivat opiskella
Kuvaus
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.
Opintosuunnitelma
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Hoito
- Jako: Ei satunnaistettu
- Inventiomalli: Yksittäinen ryhmätehtävä
- Naamiointi: Ei mitään (avoin tarra)
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
|---|---|
|
Kokeellinen: Disulfiram
description here |
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. |
Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Reduction in Complement Immunosuppressive program
Aikaikkuna: 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. |
day 0, up to 14 days
|
|
Reduction in Scavenger Immunosuppressive program
Aikaikkuna: 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. |
day 0, up to 14 days
|
Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Proportion of participants needing dexamethasone within 48 hour window
Aikaikkuna: 48 hours
|
Change in investigator-rated edema symptom composite score from baseline to Day 2 on therapy. |
48 hours
|
|
Safety of disulfiram
Aikaikkuna: 14 days
|
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)
Aikaikkuna: day 0, up to 14 days
|
Change in ESCS is analyzed using a Wilcoxon signed-rank test |
day 0, up to 14 days
|
|
Tolerability of disulfiram
Aikaikkuna: 14 days
|
Tolerability as measured by participant toxicity rates. |
14 days
|
|
Change in Microglial Inflammatory program scores
Aikaikkuna: day 0, up to 14 days
|
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
Aikaikkuna: day 0, up to 14 days
|
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
|
Yhteistyökumppanit ja tutkijat
Sponsori
Tutkijat
- Päätutkija: Tiffany Hodges, MD, University Hospitals Cleveland Medical Center
Opintojen ennätyspäivät
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Arvioitu)
Ensisijainen valmistuminen (Arvioitu)
Opintojen valmistuminen (Arvioitu)
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen Lähetetty (Todellinen)
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeksi vahvistettu
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Avainsanat
Muita asiaankuuluvia MeSH-ehtoja
Muut tutkimustunnusnumerot
- CASE7326
Yksittäisten osallistujien tietojen suunnitelma (IPD)
Aiotko jakaa yksittäisten osallistujien tietoja (IPD)?
IPD-suunnitelman kuvaus
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-jaon aikakehys
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-jaon käyttöoikeuskriteerit
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-jakamista tukeva tietotyyppi
- STUDY_PROTOCOL
- MAHLA
- ICF
- ANALYTIC_CODE
Lääke- ja laitetiedot, tutkimusasiakirjat
Tutkii yhdysvaltalaista FDA sääntelemää lääkevalmistetta
Tutkii yhdysvaltalaista FDA sääntelemää laitetuotetta
Yhdysvalloissa valmistettu ja sieltä viety tuote
Nämä tiedot haettiin suoraan verkkosivustolta clinicaltrials.gov ilman muutoksia. Jos sinulla on pyyntöjä muuttaa, poistaa tai päivittää tutkimustietojasi, ota yhteyttä register@clinicaltrials.gov. Heti kun muutos on otettu käyttöön osoitteessa clinicaltrials.gov, se päivitetään automaattisesti myös verkkosivustollemme .