Disulfiram and Copper Gluconate With Temozolomide in Unmethylated Glioblastoma Multiforme

NCT03363659 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: 17.56
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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 Disulfiram (DSF) + Copper (Cu) combination when added to standard Temozolomide in the treatment of unmethylated Glioblastoma Multiforme (GBM) patients.

Conditions

Glioblastoma; Glioblastoma Multiforme

Keywords

Glioblastoma; Glioblastoma Multiforme; Anaplastic Glioma; Unmethylated

Outcome Measures

Primary Outcomes (2)

• 6 Months Progression Free Survival (PFS)

  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.

  6 months

• Overall Survival

  Overall Survival will be assessed as a number of participants alive at 1 and 2 years.

  1 and 2 years

Secondary Outcomes (1)

• Quality of Life (QOL)

  1 year

Study Arms (1)

DSF-Cu with temozolomide and radiation

EXPERIMENTAL

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

Drug: Disulfiram; Dietary Supplement: Copper gluconate; Drug: Temozolomide

Interventions

Disulfiram DRUG

Disulfiram is taken orally, twice daily.

Also known as: Antabuse

DSF-Cu with temozolomide and radiation

Copper gluconate DIETARY_SUPPLEMENT

Copper gluconate is taken orally, twice daily

DSF-Cu with temozolomide and radiation

Temozolomide DRUG

Temozolomide is taken once daily

Also known as: Temodar, Temodal, Temcad

DSF-Cu with temozolomide and radiation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead

Study Sites (1)

Aurora Health Care, Aurora St. Luke's Medical Center

Milwaukee, Wisconsin, 53215, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

Disulfiram; Gluconates; Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Ditiocarb; Thiocarbamates; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Disulfides; Sulfides; Sulfur Compounds; Sugar Acids; Hydroxy Acids; Carbohydrates; Dacarbazine; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Manager of Oncology research
• Organization: Advocate Aurora Health

karen.cheek@aah.org

414 778 4345

Study Officials

• Asadullah Khan, MD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2017
• First Posted: December 6, 2017
• Study Start: March 28, 2018
• Primary Completion: January 13, 2022
• Study Completion: January 13, 2022
• Last Updated: October 3, 2024
• Results First Posted: September 8, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)