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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01907165
First Posted: July 24, 2013
Last Update Posted: March 16, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Washington University School of Medicine
  Purpose
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.

Condition Intervention Phase
Glioblastoma Drug: Temozolomide Drug: Disulfiram Dietary Supplement: Copper gluconate Early Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pharmacodynamic Study of Proteasome Inhibition by Disulfiram in Patients With Glioblastoma

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Pharmacological effect of disulfiram in GBM patients [ Time Frame: 30 days ]
    Degree of proteasome inhibition in peripheral white blood cells and rate of complete inhibition in GBM patients using descriptive statistics


Secondary Outcome Measures:
  • Local tumor control probabilities [ Time Frame: 2 years ]
    The Kaplan-Meier product-limit method will be used.

  • Time to tumor progression [ Time Frame: 2 years ]
    Modeled using the Cox proportional hazard models.


Enrollment: 21
Actual Study Start Date: October 10, 2013
Estimated Study Completion Date: March 31, 2018
Primary Completion Date: November 10, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Maintenance Temozolomide + Disulfram

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
Other Name: Temodar
Drug: Disulfiram
Other Name: Antabuse
Experimental: Maintenance Temozolomide + Disulfiarm + Copper Gluconate

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
Other Name: Temodar
Drug: Disulfiram
Other Name: Antabuse
Dietary Supplement: Copper gluconate

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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:

    • 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.
  • Able to understand and willing to sign an IRB-approved written informed consent document (legally authorized representative permitted).

Exclusion Criteria:

  • 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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01907165


Locations
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Jiayi Huang, M.D. Washington University School of Medicine
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01907165     History of Changes
Other Study ID Numbers: 201308038
First Submitted: July 19, 2013
First Posted: July 24, 2013
Last Update Posted: March 16, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Dacarbazine
Copper
Disulfiram
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs
Alcohol Deterrents
Acetaldehyde Dehydrogenase Inhibitors
Enzyme Inhibitors


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