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

Sponsor
Washington University School of Medicine (Other)
Overall Status
Completed
CT.gov ID
NCT01907165
Collaborator
(none)
21
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52
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Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Early Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
21 participants
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
Actual Study Start Date :
Oct 10, 2013
Actual Primary Completion Date :
Nov 10, 2016
Actual Study Completion Date :
Feb 9, 2018

Arms and Interventions

Arm Intervention/Treatment
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 Names:
  • Temodar
  • Drug: Disulfiram
    Other Names:
  • 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 Names:
  • Temodar
  • Drug: Disulfiram
    Other Names:
  • Antabuse
  • Dietary Supplement: Copper gluconate

    Outcome Measures

    Primary Outcome Measures

    1. Pharmacological effect of disulfiram in GBM patients [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

    1. Local tumor control probabilities [2 years]

      The Kaplan-Meier product-limit method will be used.

    2. Time to tumor progression [2 years]

      Modeled using the Cox proportional hazard models.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Locations

    Site City State Country Postal Code
    1 Washington University School of Medicine Saint 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

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Washington University School of Medicine
    ClinicalTrials.gov Identifier:
    NCT01907165
    Other Study ID Numbers:
    • 201308038
    First Posted:
    Jul 24, 2013
    Last Update Posted:
    Jul 20, 2018
    Last Verified:
    Jul 1, 2018
    Individual Participant Data (IPD) Sharing Statement:
    No
    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:

    Study Results

    No Results Posted as of Jul 20, 2018