Status:
TERMINATED
Disulfiram and Copper Gluconate With Temozolomide in Unmethylated Glioblastoma Multiforme
Lead Sponsor:
Wake Forest University Health Sciences
Conditions:
Glioblastoma
Glioblastoma Multiforme
Eligibility:
All Genders
18+ years
Phase:
PHASE2
Brief 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 s...
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 radioth...
Eligibility Criteria
Inclusion
- 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)
- Eastern Cooperative Oncology Group Performance Status (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 (microliter)
- Platelets ≥ 100,000/mcL
- Hemoglobin \> 10.0 g/dL (grams/deciliter) (transfusion and/or ESA (erythropoiesis-stimulating agent) 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
- 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 international normalized ratio (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
Key Trial Info
Start Date :
March 28 2018
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
January 13 2022
Estimated Enrollment :
15 Patients enrolled
Trial Details
Trial ID
NCT03363659
Start Date
March 28 2018
End Date
January 13 2022
Last Update
October 3 2024
Active Locations (1)
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1
Aurora Health Care, Aurora St. Luke's Medical Center
Milwaukee, Wisconsin, United States, 53215