Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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.
 
ClinicalTrials.gov Identifier: NCT01907165
Recruitment Status : Completed
First Posted : July 24, 2013
Last Update Posted : July 20, 2018
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine

Tracking Information
First Submitted Date  ICMJE July 19, 2013
First Posted Date  ICMJE July 24, 2013
Last Update Posted Date July 20, 2018
Actual Study Start Date  ICMJE October 10, 2013
Actual Primary Completion Date November 10, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 19, 2013)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 19, 2013)
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Disulfiram in Treating Patients With Glioblastoma Multiforme After Radiation Therapy With Temozolomide
Official Title  ICMJE A Pharmacodynamic Study of Proteasome Inhibition by Disulfiram in Patients With Glioblastoma
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Glioblastoma
Intervention  ICMJE
  • Drug: Temozolomide
    Other Name: Temodar
  • Drug: Disulfiram
    Other Name: Antabuse
  • Dietary Supplement: Copper gluconate
Study Arms  ICMJE
  • 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.

    Interventions:
    • Drug: Temozolomide
    • Drug: Disulfiram
  • 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.

    Interventions:
    • Drug: Temozolomide
    • Drug: Disulfiram
    • Dietary Supplement: Copper gluconate
Publications * Karamanakos PN. Possible role for furazolidone in the treatment of glioblastoma multiforme. J BUON. 2013 Oct-Dec;18(4):1097.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 14, 2017)
21
Original Estimated Enrollment  ICMJE
 (submitted: July 19, 2013)
12
Actual Study Completion Date  ICMJE February 9, 2018
Actual Primary Completion Date November 10, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01907165
Other Study ID Numbers  ICMJE 201308038
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Washington University School of Medicine
Study Sponsor  ICMJE Washington University School of Medicine
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jiayi Huang, M.D. Washington University School of Medicine
PRS Account Washington University School of Medicine
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP