Disulfiram and Chelated Zinc for the Rx of Disseminated Mets Mel That Has Failed First Line Therapy

Study Overview
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Brief Summary
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Primary Objectives Determine the response rate associated with treatment of refractory disseminated malignant melanoma with disulfiram and chelated zinc. Secondary Objectives Determine the progression-free survival associated with treatment of refractory disseminated malignant melanoma with disulfiram and chelated zinc. Determine the overall survival associated with treatment of refractory disseminated malignant melanoma with disulfiram and chelated zinc. Determine the toxicity associated with treatment of refractory disseminated malignant melanoma with disulfiram and chelated zinc Determine the effect of disulfiram and chelated zinc on in vivo protein S-glutathionylation.

Conditions
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Melanoma

Intervention / Treatment
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* Drug: disulfiram and chelated zinc


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subjects must fulfill all the following inclusion criteria to be eligible for participation in the study, unless otherwise specified: Male and female patients with stage IV melanoma cancer with biopsy proven metastases demonstrated by imaging studies. Extent of disease should be documented by CT scanning of the chest, abdomen and pelvis, or PET/CT scanning. At least one site of disease should be measurable by RECIST criteria. Age of 18 years or more ECOG performance status of 0 - 2 Patients must have received and progressed after or not responded to at least one cycle of first line therapy (chemotherapy, biotherapy, or biochemotherapy) or are unwilling or ineligible to undergo standard therapy Patients with brain metastases along with disease at other sites are eligible to participate if their brain disease has been treated with surgery or radiation Not currently receiving other cancer chemotherapy Not currently participating in another study Baseline AST and ALT not greater than 2.0 X upper limit of normal Able and willing to provide informed consent and to comply with study procedures Able to ingest oral medications No known allergy to disulfiram or zinc gluconate Willing to refrain from ingestion of alcoholic beverages while on the study Serum copper within the normal range at baseline, or if outside the normal range, the PI will review for clinical significance Exclusion Criteria: Potential study subjects who meet any of the following criteria are not eligible for participation in the study: Participation in another clinical trial of a therapeutic drug during the past 30 days Addiction to alcohol or cocaine Baseline AST or ALT greater than 2.0 X upper limit of normal Unable to ingest oral medications Unable to undergo CT scanning because of inability to lie recumbent in the scanner; Actively receiving cytotoxic cancer chemotherapy agents Evidence of thiuram allergy (may present as contact allergy to rubber or elastic) Current use of sertraline and cyclosporine Women of child-bearing potential who are not using a commonly accepted effective means of contraception; women of child-bearing potential will have a pregnancy test before enrollment Need for warfarin or theophylline, the metabolism of which is likely influenced by disulfiram Pregnant women and nursing mothers are not allowed to enroll on this study Patients who are taking medications metabolized by cytochrome P450 2E1, including chlorzoxazone or halothane and its derivatives

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 |
| --- | --- |
| Other: Disulfiram and chelated zinc<br>There is only one arm. All patients are treated wtih disulfiram and chelated zinc. | Drug: disulfiram and chelated zinc<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate to Treatment of Melanoma With Disulfiram and Chelated Zinc | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT scanning of the chest, abdomen and pelvis, or PET/CT scanning.: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | Response to treatment will be measured by RECIST evaluation at disease assessment time-points from date of randomization until the date of first documented progression or death from any cause whichever came first (up to 15 months.) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival |  | Every 56 days - for up to two years |