Safety, Tolerability and Efficacy of Disulfiram and Copper Gluconate in Recurrent Glioblastoma

Study Overview
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Brief Summary
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This study of DSF-Cu in combination with TMZ for recurrent GBM will evaluate the antitumor effect in patients who have recurrent GBM. Patients will take DSF-Cu daily during their routine standard of care with TMZ therapy for approximately 6 months. Patients will be evaluated for response every 8 weeks. Patients will be followed up 2 years after the last dose of DSF-Cu.

Official Title
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A Phase II, Multicenter, Open-Label, Single-Arm Study to Evaluate the Safety, Tolerability, and Efficacy of DIsulfiram and Copper Gluconate in Recurrent Glioblastoma

Conditions
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Recurrent Glioblastoma

Intervention / Treatment
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* Drug: Disulfiram/Copper
* Drug: Temozolomide (TMZ)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed GBM (WHO grade IV). The subject must have completed RT with concurrent TMZ at least 12 weeks prior to the planned start of treatment on this study UNLESS there is pathological verification of recurrent tumor and at least 4 weeks have elapsed since the end of RT with concurrent TMZ. Experienced first unequivocal progression of tumor by magnetic resonance imaging (MRI) [as assessed via Radiologic Assessment in Neuro-Oncology (RANO) criteria within 3 months from the last dose of TMZ. Karnofsky performance status (KPS) of at least 60%. Willing to remain abstinent from consuming alcohol. Recovered from the toxic effects of prior therapy to < grade 2 toxicity per NCI CTCAE prior to study registration (except lymphopenia). Meets laboratory criteria for the following parameters: ANC, platelets, hemoglobin, total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, BUN and creatinine. 11. Females of childbearing potential must be willing to use an acceptable method of birth control (i.e., intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. Exclusion Criteria: Radiographic evidence of leptomeningeal dissemination, gliomatosis cerebri, infratentorial tumor, or disease at sites remote from the supratentorial brain. Enrolled in another clinical trial testing a novel therapy or drug within the past 4 weeks. Received more than one course of radiation therapy or more than a total dose of 75 Gy. History of allergic reaction/hypersensitivity to temozolomide, dacarbazine, DSF or Cu. Treatment with the following medications are contraindicated with DSF: metronidazole, isoniazid, dronabinol, carbocisteine, lopinavir, paraldehyde, ritonavir, sertraline, tindazole, tizanidine, atazanavir. Fever within 3 days prior to study enrollment. Active or severe hepatic or renal disease. Grade 2 or higher peripheral neuropathy or ataxia per NCI CTCAE History of idiopathic seizure disorder schizophrenia, or psychosis unrelated to glioblastoma, corticosteroid, or anti-epileptic medications. History of Wilson's disease. History of hemochromatosis. Pregnant or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DSF-Cu<br>Disulfiram/copper (oral capsules) dosed 80 mg/1.5 mg three times a day for approximately 6 months. | Drug: Disulfiram/Copper<br>* Disulfiram/copper gluconate is taken three times a day.<br>Drug: Temozolomide (TMZ)<br>* TMZ is given per standard of care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | ORR will be defined as the percentage of patients with complete response (CR) or partial response (PR) according to the RANO criteria. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Percentage of patients that are free from progressive disease per RANO criteria | 6 months | 
| Overall Survival | Percentage of patients that are alive | 6 months and 12 months | 
| Number of Participants With Serious Adverse Events | Number of Participants with Grade 3 and 4 serious adverse events | 14 months | 
| Median Progression Free Survival | Duration of progression free survival according to RANO criteria | 12 months | 
| Median Duration of Overall Survival | Duration of overall survival for patients that are alive | 14 months |