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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Utah
ClinicalTrials.gov Identifier:
NCT00742911
First received: August 26, 2008
Last updated: July 23, 2013
Last verified: July 2013
  Purpose

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.

Condition Intervention Phase
Cancer
Drug: Disulfiram
Drug: Copper Gluconate
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Disulfiram and Copper Gluconate for the Treatment of Refractory Solid Tumors Involving the Liver

Resource links provided by NLM:


Further study details as provided by University of Utah:

Primary Outcome Measures:
  • 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 [ Time Frame: July 2011 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Determine if disulfiram and copper gluconate induce measurable responses for the treatment of hepatic metastases from solid tumors [ Time Frame: July 2011 ] [ Designated as safety issue: No ]
  • Qualitative assessment of the induction of S-glutathionylation in proteins of circulating leukocytes in patients treated with disulfiram and copper gluconate [ Time Frame: July 2011 ] [ Designated as safety issue: Yes ]

Enrollment: 21
Study Start Date: July 2008
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: Disulfiram

Patients will take a pill of disulfiram at a fixed dose of 250 mg with their evening meal. This dose of disulfiram used to treat alcoholism. We will start by administering 2 mg of copper as copper gluconate along with 250 mg disulfiram.

Patients must not consume beverages containing alcohol while taking disulfiram.

Other Names:
  • Chemical Name: tetraethylthiuram disulfide
  • Other names: Antabuse
Drug: Copper Gluconate

Commercially available. Copper gluconate has long been manufactured and sold as a food supplement. Copper gluconate should be taken separately from disulfiram, and if possible with breakfast.

Copper gluconate should not be administered to individuals with Wilson's disease or a family history of Wilson's disease.

Patients will receive 2 mg, 4mg, 6mg or 8mg daily

Other Names:
  • Chemical Name: copper gluconate
  • Other names: none

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00742911

Locations
United States, Utah
Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
University of Utah
Investigators
Principal Investigator: Kenneth Grossmann, MD, PhD Huntsman Cancer Institute
  More Information

No publications provided

Responsible Party: University of Utah
ClinicalTrials.gov Identifier: NCT00742911     History of Changes
Other Study ID Numbers: HCI26679
Study First Received: August 26, 2008
Last Updated: July 23, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Utah:
Solid Tumors, Liver

Additional relevant MeSH terms:
Copper
Disulfiram
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Alcohol Deterrents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 20, 2014