Clinical trial · Interventional
Disulfiram and Copper Gluconate With Temozolomide in Unmethylated Glioblastoma Multiforme
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
NCT03363659CI-TRIAL-00081311terminatedPhase 2Results postedClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Why stopped (as posted): Investigator decision
Summary
Brief summary (as posted)
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
Conditions (2)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Glioblastoma | Glioblastoma | CURATED_BROADER | 0.80 |
| Glioblastoma Multiforme | Glioblastoma | CURATED_BROADER | 0.80 |
Interventions
Interventions (3)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Copper gluconate | Dietary Supplement | — | UNRESOLVED |
| Disulfiram | Drug | — | UNRESOLVED |
| Temozolomide | Drug | Temozolomide | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- DSF-Cu with temozolomide and radiation
- description
- 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
- interventionNames
- Drug: Disulfiram
- Dietary Supplement: Copper gluconate
- Drug: Temozolomide
Primary outcomes (2)
- measure
- 6 Months Progression Free Survival (PFS)
- timeFrame
- 6 months
- description
- 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.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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
References
Publications (0)
Data not yet available
No reference posted for this study.