Clinical Trials /

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

NCT01907165

Description:

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.

Related Conditions:
  • Glioblastoma
Recruiting Status:

Completed

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Disulfiram in Treating Patients With Glioblastoma Multiforme After Radiation Therapy With Temozolomide
  • Official Title: A Pharmacodynamic Study of Proteasome Inhibition by Disulfiram in Patients With Glioblastoma

Clinical Trial IDs

  • ORG STUDY ID: 201308038
  • NCT ID: NCT01907165

Conditions

  • Glioblastoma

Interventions

DrugSynonymsArms
TemozolomideTemodarMaintenance Temozolomide + Disulfram
DisulfiramAntabuseMaintenance Temozolomide + Disulfram

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.

Trial Arms

NameTypeDescriptionInterventions
Maintenance Temozolomide + DisulframExperimentalBeginning 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.
  • Temozolomide
  • Disulfiram
Maintenance Temozolomide + Disulfiarm + Copper GluconateExperimentalBeginning 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.
  • Temozolomide
  • Disulfiram

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Pharmacological effect of disulfiram in GBM patients
Time Frame:30 days
Safety Issue:
Description:Degree of proteasome inhibition in peripheral white blood cells and rate of complete inhibition in GBM patients using descriptive statistics

Secondary Outcome Measures

Measure:Local tumor control probabilities
Time Frame:2 years
Safety Issue:
Description:The Kaplan-Meier product-limit method will be used.
Measure:Time to tumor progression
Time Frame:2 years
Safety Issue:
Description:Modeled using the Cox proportional hazard models.

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Washington University School of Medicine

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