- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03363659
Disulfiram and Copper Gluconate With Temozolomide in Unmethylated Glioblastoma Multiforme
September 5, 2023 updated by: Aurora Health Care
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
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 Disulfiram (DSF) + Copper (Cu) combination when added to standard Temozolomide in the treatment of unmethylated Glioblastoma Multiforme (GBM) patients.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
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 Glioblastoma multiforme (GBM) patients.
Study Type
Interventional
Enrollment (Actual)
15
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Wisconsin
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Milwaukee, Wisconsin, United States, 53215
- Aurora Health Care, Aurora St. Luke's Medical Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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)
- 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 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 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: DSF-Cu with temozolomide and radiation
Disulfiram (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
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Disulfiram is taken orally, twice daily.
Other Names:
Copper gluconate is taken orally, twice daily
Temozolomide is taken once daily
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
6 Months Progression Free Survival (PFS)
Time Frame: 6 months
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To determine 6 month PFS of patients with unmethylated glioblastoma treated with DSF-Cu in combination with concurrent radiation and temozolomide.
This was assessed by the number of participants who did not have disease progression and were alive at 6 months.
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6 months
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Overall Survival
Time Frame: 1 and 2 years
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Overall Survival will be assessed as a number of participants alive at 1 and 2 years.
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1 and 2 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Quality of Life (QOL)
Time Frame: 1 year
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Edmonton Symptom Assessment System - Revised (ESAS-r) questionnaire
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1 year
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Asadullah Khan, MD, Aurora Health Care
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 28, 2018
Primary Completion (Actual)
January 13, 2022
Study Completion (Actual)
January 13, 2022
Study Registration Dates
First Submitted
November 30, 2017
First Submitted That Met QC Criteria
November 30, 2017
First Posted (Actual)
December 6, 2017
Study Record Updates
Last Update Posted (Actual)
September 8, 2023
Last Update Submitted That Met QC Criteria
September 5, 2023
Last Verified
January 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms, Glandular and Epithelial
- Astrocytoma
- Glioma
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Glioblastoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Trace Elements
- Micronutrients
- Alcohol Deterrents
- Acetaldehyde Dehydrogenase Inhibitors
- Copper
- Temozolomide
- Disulfiram
Other Study ID Numbers
- 17.56
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
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.
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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