Disulfiram in Treating Patients With Glioblastoma Multiforme After Radiation Therapy With Temozolomide

NCT01907165 | Completed Early Phase 1 DMC FDA Drug

• 1 other identifier: 201308038
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Glioblastoma

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (2)

• Local tumor control probabilities

  2 years

• Time to tumor progression

  2 years

Study Arms (2)

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.

Drug: Temozolomide; Drug: Disulfiram

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.

Drug: Temozolomide; Drug: Disulfiram; Dietary Supplement: Copper gluconate

Interventions

Temozolomide DRUG

Also known as: Temodar

Maintenance Temozolomide + Disulfiarm + Copper Gluconate; Maintenance Temozolomide + Disulfram

Disulfiram DRUG

Also known as: Antabuse

Maintenance Temozolomide + Disulfiarm + Copper Gluconate; Maintenance Temozolomide + Disulfram

Copper gluconate DIETARY_SUPPLEMENT

Maintenance Temozolomide + Disulfiarm + Copper Gluconate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Absolute neutrophil count ≥ 1,500/mcL
• Platelets ≥ 100,000/mcL
• Hemoglobin \> 9.0 g/dL (transfusion and/or ESA allowed)
• Total bilirubin ≤ 2x institutional upper limit of normal (ULN)
• AST and ALT \< 3 x ULN
• Calculated creatinine clearance must be \> 60 mL/min (by Cockcroft-Gault)
• 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.

You may not qualify if:

• Receipt of any other investigational agents within 14 days prior to study enrollment.
• Enrolled on another clinical trial testing a novel therapy or drug.
• History of allergic reaction to disulfiram.
• Treatment with clinically significant cytochromes P450 enzyme inducers, such as phenytoin, phenobarbital, chlordiazepoxide, diazepam, isoniazid, metronidazole, warfarin, amitriptyline within 14 days prior to the first dose of disulfiram. Of note, lorazepam and oxazepam are not affected by the P450 system and are not contraindicated with disulfiram.
• Active or severe hepatic, cardiovascular, or cerebrovascular disease, including myocardial infarction within 6 months prior to enrollment, have New York Heart Association (NYHA) Class III or IV heart failure (Appendix B), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
• History of idiopathic seizure disorder, psychosis or schizophrenia.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of initiation of treatment.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• Karamanakos PN. Possible role for furazolidone in the treatment of glioblastoma multiforme. J BUON. 2013 Oct-Dec;18(4):1097. No abstract available.

  PMID: 24344045 DERIVED

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Glioblastoma

Interventions

Temozolomide; Disulfiram; Gluconates

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Ditiocarb; Thiocarbamates; Carbamates; Acids, Acyclic; Carboxylic Acids; Disulfides; Sulfides; Sulfur Compounds; Sugar Acids; Hydroxy Acids; Carbohydrates

Study Officials

• Jiayi Huang, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2013
• First Posted: July 24, 2013
• Study Start: October 10, 2013
• Primary Completion: November 10, 2016
• Study Completion: February 9, 2018
• Last Updated: July 20, 2018

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)