Phase I Study of Disulfiram and Copper Gluconate for the Treatment of Refractory Solid Tumors Involving the Liver

• Status: Completed
• Trial end date: 2013-03-01
• Target enrollment: 0
• Participant gender: All

Summary

OBJECTIVES:

Primary Objectives

• Determine the safety and toxicity profile of co-administration of disulfiram and copper gluconate for the treatment of refractory malignancies that have metastasized to the liver.

Secondary Objectives

• Determine if disulfiram and copper gluconate induce measurable responses for the treatment of hepatic metastases from solid tumors.

• Qualitative assessment of the induction of S-glutathionylation in proteins of circulating leukocytes in patients treated with disulfiram and copper gluconate.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Utah
• Treatments: Copper; Disulfiram

Criteria

Inclusion Criteria:

The subjects must fulfill all the following inclusion criteria to be eligible for participation in the study, unless otherwise specified:

1. Male and female patients with stage IV cancer with metastases demonstrated on abdominal computed tomography (CT) or MRI imaging; patients may have metastatic disease at other sites than the liver, but should have hepatic metastases in order to be eligible for enrollment on this study. Patients are eligible irrespective of the histologic origin of their malignancy but should have exhausted or be unwilling to undergo standard treatment approaches. If a primary histologic diagnosis of malignancy has not been established, hepatic metastases will have to be biopsy proven. Liver disease should be measurable by RECIST criteria.

2. Age of 18 years or more;

3. ECOG performance status of 0 - 2;

4. Patients must have exhausted all standard avenues of therapy for their cancer if such therapy is available, or should be unwilling to undergo such therapy;

5. Not currently receiving other cancer chemotherapy;

6. Not currently participating in another study;

7. Anticipated survival of at least 3 months;

8. Baseline AST and ALT not greater than 2.5 X upper limit of normal;

9. Serum copper within normal limits

10. Serum ceruloplasmin > 17 mg/dL;

11. Able and willing to provide informed consent and to comply with study procedures;

12. Able to ingest oral medications;

13. No known allergy to disulfiram or copper gluconate;

14. Willing to refrain from ingestion of alcoholic beverages while on the study.

Exclusion Criteria:

Potential study subjects who meet any of the following criteria are not eligible for participation in the study:

1. Participation in another clinical trial of a therapeutic drug during the past 30 days;

2. Addiction to alcohol or cocaine;

3. Baseline AST or ALT greater than 2.5 X upper limit of normal;

4. Unable to ingest oral medications;

5. Unable to undergo CT scanning because of inability to lie recumbent in the scanner;

6. Actively receiving cytotoxic cancer chemotherapy agents;

7. Anticipated survival of less than 3 months;

8. 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.

9. History of active liver disease, including chronic active hepatitis, viral hepatitis (hepatitis B, C and CMV), cholestatic jaundice from any etiology, toxic hepatitis, or cholestatic hepatitis or jaundice with bilirubin greater than 2.0 X upper limit of normal;

10. History of Wilson's disease or family member with Wilson's disease;

11. History of hemochromatosis or family member with hemochromatosis;

12. History of other iron overload syndrome such as hemochromatosis.

13. Need for warfarin or theophylline, the metabolism of which is likely influenced by disulfiram.

14. Pregnant women and nursing mothers are not allowed to enroll on this study.

15. Patients who are taking medications metabolized by cytochrome P450 2E1, including chlorzoxazone or halothane and its derivatives.