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

NCT00742911 | Completed Phase 1 DMC

• 1 other identifier: HCI26679
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cancer

Keywords

Solid Tumors, Liver

Outcome Measures

Primary Outcomes (1)

• 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

  July 2011

Secondary Outcomes (2)

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

  July 2011

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

  July 2011

Study Arms (1)

1

EXPERIMENTAL

Drug: Disulfiram; Drug: Copper Gluconate

Interventions

Disulfiram DRUG

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.

Also known as: Chemical Name: tetraethylthiuram disulfide, Other names: Antabuse

1

Copper Gluconate DRUG

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

Also known as: Chemical Name: copper gluconate, Other names: none

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Age of 18 years or more;
• ECOG performance status of 0 - 2;
• 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;
• Not currently receiving other cancer chemotherapy;
• Not currently participating in another study;
• Anticipated survival of at least 3 months;
• Baseline AST and ALT not greater than 2.5 X upper limit of normal;
• Serum copper within normal limits
• Serum ceruloplasmin \> 17 mg/dL;
• Able and willing to provide informed consent and to comply with study procedures;
• Able to ingest oral medications;
• No known allergy to disulfiram or copper gluconate;
• Willing to refrain from ingestion of alcoholic beverages while on the study.

You may not qualify if:

• 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 2.5 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;
• Anticipated survival of less than 3 months;
• 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.
• 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;
• History of Wilson's disease or family member with Wilson's disease;
• History of hemochromatosis or family member with hemochromatosis;
• History of other iron overload syndrome such as hemochromatosis.
• 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.

Sponsors & Collaborators

• University of Utah: lead

Study Sites (1)

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• Kelley KC, Grossman KF, Brittain-Blankenship M, Thorne KM, Akerley WL, Terrazas MC, Kosak KM, Boucher KM, Buys SS, McGregor KA, Werner TL, Agarwal N, Weis JR, Sharma S, Ward JH, Kennedy TP, Sborov DW, Shami PJ. A Phase 1 dose-escalation study of disulfiram and copper gluconate in patients with advanced solid tumors involving the liver using S-glutathionylation as a biomarker. BMC Cancer. 2021 May 7;21(1):510. doi: 10.1186/s12885-021-08242-4.

  PMID: 33957901 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

Disulfiram; Gluconates

Intervention Hierarchy (Ancestors)

Ditiocarb; Thiocarbamates; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Disulfides; Sulfides; Sulfur Compounds; Sugar Acids; Hydroxy Acids; Carbohydrates

Study Officials

• Kenneth Grossmann, MD, PhD

  Huntsman Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2008
• First Posted: August 28, 2008
• Study Start: July 1, 2008
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: October 31, 2014

Record last verified: 2014-10

Locations

US (1)