Disulfiram and Copper Gluconate With Temozolomide in Unmethylated Glioblastoma Multiforme
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| ClinicalTrials.gov Identifier: NCT03363659 |
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Recruitment Status :
Recruiting
First Posted : December 6, 2017
Last Update Posted : March 13, 2019
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Sponsor:
Aurora Health Care
Information provided by (Responsible Party):
Aurora Health Care
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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 study evaluates the impact of DSF + Cu combination when added to standard Temozolomide in the treatment of unmethylated GBM patients.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Glioblastoma Glioblastoma Multiforme | Drug: Disulfiram Dietary Supplement: Copper gluconate Drug: Temozolomide | Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 40 participants |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | March 28, 2018 |
| Estimated Primary Completion Date : | March 31, 2019 |
| Estimated Study Completion Date : | March 31, 2021 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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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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Drug: Disulfiram
Disulfiram is taken orally, twice daily.
Other Name: Antabuse Dietary Supplement: Copper gluconate Copper gluconate is taken orally, twice daily Drug: Temozolomide Temozolomide is taken once daily
Other Name: Temodar, Temodal, Temcad |
Primary Outcome Measures :
- Progression Free Survival (PFS) [ Time Frame: 6 months ]
- Overall Survival [ Time Frame: 1 and 2 years ]
Secondary Outcome Measures :
- Quality of life (QOL) [ Time Frame: 1 year ]Edmonton Symptom Assessment System - Revised (ESAS-r) questionnaire
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
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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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03363659
Contacts
| Contact: Kate McPolin, RN | 414-385-7125 | kate.mcpolin@aurora.org | |
| Contact: Carol Tutino, RN,MS,CCRC | 414-649-5526 | carol.tutino@aurora.org |
Locations
| United States, Wisconsin | |
| Aurora Health Care, Aurora St. Luke's Medical Center | Recruiting |
| Milwaukee, Wisconsin, United States, 53215 | |
| Contact: Lynda Yanny 414-649-6685 lynda.yanny@aurora.org | |
| Principal Investigator: George Bobustuc, MD | |
| Sub-Investigator: Richard A Rovin, MD | |
| Sub-Investigator: Asad Khan, MD | |
| Sub-Investigator: Amin Kassam, MD | |
| Sub-Investigator: Santhi Konduri, PhD | |
Sponsors and Collaborators
Aurora Health Care
Investigators
| Principal Investigator: | George Bobustuc, MD | Aurora Health Care |
| Responsible Party: | Aurora Health Care |
| ClinicalTrials.gov Identifier: | NCT03363659 History of Changes |
| Other Study ID Numbers: |
17.56 |
| First Posted: | December 6, 2017 Key Record Dates |
| Last Update Posted: | March 13, 2019 |
| Last Verified: | March 2019 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| 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 | |
Keywords provided by Aurora Health Care:
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Glioblastoma Glioblastoma Multiforme Anaplastic Glioma Unmethylated |
Additional relevant MeSH terms:
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Glioblastoma Astrocytoma Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Temozolomide Copper Disulfiram |
Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Trace Elements Micronutrients Nutrients Growth Substances Physiological Effects of Drugs Alcohol Deterrents Acetaldehyde Dehydrogenase Inhibitors Enzyme Inhibitors |