Disulfiram and Copper Gluconate With Temozolomide in Unmethylated Glioblastoma Multiforme

• Status: Active, not recruiting
• Trial end date: 2022-12-31
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Aurora Health Care
• Treatments: Copper; Disulfiram; Temozolomide

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