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This clinical trial studies disulfiram in treating patients with glioblastoma multiforme (GBM) who have completed radiation therapy with temozolomide. Disulfiram may block some of the enzymes needed for tumor cell growth and improve clinical outcome in GBM patients.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Maintenance Temozolomide + Disulfram | Experimental | Beginning 4-6 weeks after completion of radiation therapy, patients receive maintenance temozolomide 150-200 mg/m2 PO QD on Days 1-5 every 28 days for 6 months. Disulfiram (dose level 0 = 500 mg PO QD or dose level 1 1000 mg PO QD) on days 1-28. Treatment repeats every 28 days for 6 courses* in the absence of disease progression or unacceptable toxicity. NOTE: *Patients may receive additional maintenance temozolomide at the discretion of the treating medical oncologist. |
|
| Maintenance Temozolomide + Disulfiarm + Copper Gluconate | Experimental | Beginning 4-6 weeks after completion of radiation therapy, patients receive maintenance temozolomide 150-200 mg/m2 PO QD on Days 1-5 every 28 days for 6 months, disulfiram 500 mg PO QD (dose of disulfiram determined to be the MTD) on Days 1-28, and copper gluconate 6 mg PO QD on Days 1-28. Treatment repeats every 28 days for 6 courses* in the absence of disease progression or unacceptable toxicity. NOTE: *Patients may receive additional maintenance temozolomide at the discretion of the treating medical oncologist. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Temozolomide | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacological effect of disulfiram in GBM patients | Degree of proteasome inhibition in peripheral white blood cells and rate of complete inhibition in GBM patients using descriptive statistics | 30 days |
| Measure | Description | Time Frame |
|---|---|---|
| Local tumor control probabilities | The Kaplan-Meier product-limit method will be used. | 2 years |
| Time to tumor progression | Modeled using the Cox proportional hazard models. |
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Inclusion Criteria:
Diagnosis of histologically confirmed GBM (WHO grade IV).
At least 18 years of age.
ECOG performance status of at least 2.
Has received or is in the process of completing a course of definitive radiotherapy of at least 45 Gy with concurrent temozolomide (patient may be registered before completing radiotherapy as long as it is anticipated that s/he will complete at least 45 Gy).
Eligible for and planning to receive maintenance temozolomide after completion of definitive radiotherapy plus temozolomide.
Willing to remain abstinent from consuming alcohol while on disulfiram.
Meets the following laboratory criteria:
Females of childbearing potential (defined as a female who is non-menopausal or surgically sterilized) must be willing to use an acceptable method of birth control (i.e., hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
Able to take oral medication.
Able to understand and willing to sign an IRB-approved written informed consent document (legally authorized representative permitted).
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jiayi Huang, M.D. | Washington University School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24344045 | Derived | Karamanakos PN. Possible role for furazolidone in the treatment of glioblastoma multiforme. J BUON. 2013 Oct-Dec;18(4):1097. No abstract available. |
| Label | URL |
|---|---|
| Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine | View source |
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| ID | Term |
|---|---|
| D005909 | Glioblastoma |
| ID | Term |
|---|---|
| D001254 | Astrocytoma |
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
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| ID | Term |
|---|---|
| D000077204 | Temozolomide |
| D004221 | Disulfiram |
| D005942 | Gluconates |
| ID | Term |
|---|---|
| D003606 | Dacarbazine |
| D014226 | Triazenes |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
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| Disulfiram | Drug |
|
|
| Copper gluconate | Dietary Supplement |
|
| 2 years |
| D009373 |
| Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| D001393 |
| Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D004050 | Ditiocarb |
| D013859 | Thiocarbamates |
| D002219 | Carbamates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D004220 | Disulfides |
| D013440 | Sulfides |
| D013457 | Sulfur Compounds |
| D013400 | Sugar Acids |
| D006880 | Hydroxy Acids |
| D002241 | Carbohydrates |