Clinical Trials /

Disulfiram and Copper Gluconate With Temozolomide in Unmethylated Glioblastoma Multiforme

NCT03363659

Description:

One of Disulfiram antitumor effects suggested in preclinical studies is MGMT (methyl-guanine-methyl-transferase) inhibition. Disulfiram MGMT inhibitory effect is enhanced by addition of Copper. This study evaluates the impact of DSF + Cu combination when added to standard Temozolomide in the treatment of unmethylated GBM patients.

Related Conditions:
  • Glioblastoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Disulfiram and Copper Gluconate With Temozolomide in Unmethylated Glioblastoma Multiforme
  • Official Title: A Phase II, Open-Label Study to Evaluate the Safety, Tolerability, and Efficacy of Disulfiram and Copper Gluconate When Added to Standard Temozolomide Treatment in Patients With Newly Diagnosed Resected Unmethylated Glioblastoma Multiforme

Clinical Trial IDs

  • ORG STUDY ID: 17.56
  • NCT ID: NCT03363659

Conditions

  • Glioblastoma
  • Glioblastoma Multiforme

Interventions

DrugSynonymsArms
DisulfiramAntabuseDSF-Cu with temozolomide and radiation
TemozolomideTemodar, Temodal, TemcadDSF-Cu with temozolomide and radiation

Purpose

One of Disulfiram antitumor effects suggested in preclinical studies is MGMT (methyl-guanine-methyl-transferase) inhibition. Disulfiram MGMT inhibitory effect is enhanced by addition of Copper. This study evaluates the impact of DSF + Cu combination when added to standard Temozolomide in the treatment of unmethylated GBM patients.

Detailed Description

      Glioblastoma is the most common malignant primary brain tumor and one of the most devastating
      cancers. The current standard of care for glioblastoma includes maximal safe resection
      followed by radiotherapy and temozolomide, which results in a median progression-free
      survival of less than 7 months, and median overall survival (OS) of less than 15 months.
      Moreover, patients with unmethylated glioblastoma respond poorly to this current standard
      treatment. This clinical trial evaluates the potential role of continuous, upfront use of
      Disulfiram in combination with Copper gluconate in enhancing temozolomide effect in the
      treatment of unmethylated GBM patients.
    

Trial Arms

NameTypeDescriptionInterventions
DSF-Cu with temozolomide and radiationExperimentalDisulfiram (DSF; oral) / copper gluconate (Cu; oral) dosed at 125 mg / 2 mg, twice daily. Temozolomide will be administered following the standard Stupp protocol at a dose of 75 mg/m2 for 42 days with concurrent radiation therapy. Temozolomide maintenance dose will be 150 mg/m2 once daily on Days 1-5 of every 28-day cycle while DSF-Cu is continued twice daily, as tolerated, for the duration of the Temozolomide adjuvant treatment. Patients demonstrating continued benefit from the adjuvant temozolomide after 6 cycles can continue treatment to a maximum of 12 cycles
  • Disulfiram
  • Temozolomide

Eligibility Criteria

        Inclusion Criteria:

          -  Age 18 or older

          -  Diagnosis of histologically confirmed glioblastoma (WHO grade IV). Subjects with an
             original histologic diagnosis of low grade glioma or anaplastic glioma (WHO grade II
             or III) are eligible if a subsequent histological diagnosis of glioblastoma is made

          -  Patients whose tumor is determined to be unmethylated

          -  Patients with incomplete resection as determined by residual, measurable gadolinium or
             contrast-enhancing lesion or lesions

          -  Recent resection of glioblastoma within 4 weeks of study entry. Patients who have only
             had a tumor biopsy and who are considered unresectable are eligible (but based on the
             study accrual this subset of patients with unresectable tumor may be considered for
             separate analysis)

          -  ECOG PS of ≤ 2 (see appendix A)

          -  Willing to remain abstinent from consuming alcohol while on DSF

          -  No prior radiation or chemotherapy

          -  Meets the following laboratory criteria:

               -  Absolute neutrophil count ≥ 1,500/mcL

               -  Platelets ≥ 100,000/mcL

               -  Hemoglobin > 10.0 g/dL (transfusion and/or ESA allowed)

               -  Total bilirubin and alkaline phosphatase ≤ 2x institutional upper limit of normal
                  (ULN)

               -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x ULN

               -  Blood urea nitrogen (BUN) and creatinine < 1.5 x ULN

          -  Able to take oral medication

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

        Exclusion Criteria:

          -  Radiographic evidence of leptomeningeal dissemination, extensive intraparenchymal
             dissemination, infratentorial tumor, or metastatic disease to sites remote from the
             supratentorial brain

          -  Enrolled in another clinical trial testing a novel therapy or drug

          -  Received prior radiation therapy or chemotherapy for glioblastoma

          -  History of allergic reaction/hypersensitivity to DSF (without alcohol) or copper.

          -  Treatment with the following medications that may interfere with metabolism of DSF:
             warfarin (unless otherwise chosen by the study PI who will actively adjust Coumadin
             dose to consistently maintain a safe, therapeutic INR < 3), theophylline,
             amitriptyline, isoniazid, metronidazole, phenytoin, phenobarbital, chlorzoxazone,
             halothane, imipramine, chlordiazepoxide, diazepam. (Note: lorazepam and oxazepam are
             not affected by the P450 system and are not contraindicated with DSF).

          -  Active severe hepatic or renal disease

          -  Grade 2 or higher peripheral neuropathy or ataxia per NCI CTCAE version 4.0 (2009)

          -  History of idiopathic seizure disorder schizophrenia, or psychosis unrelated to
             glioblastoma, corticosteroid, or anti-epileptic medications

          -  History of Wilson's or Gilbert's disease

          -  Current excessive use of alcohol
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:6 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Quality of life (QOL)
Time Frame:1 year
Safety Issue:
Description:Edmonton Symptom Assessment System - Revised (ESAS-r) questionnaire

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Aurora Health Care

Trial Keywords

  • Glioblastoma
  • Glioblastoma Multiforme
  • Anaplastic Glioma
  • Unmethylated

Last Updated

April 29, 2019