Phase II Trial of Disulfiram With Copper in Metastatic Breast Cancer (DISC)

July 16, 2025 updated by: The Institute of Molecular and Translational Medicine, Czech Republic

Phase II Open Labeled Trial of Disulfiram With Copper in Metastatic Breast Cancer

The aim of the study is to establish clinical evidence for introducing disulfiram and cooper as an active therapy for metastatic breast cancer upon failure of conventional systemic and/or locoregional therapies.

Analyses of the following objectives will be performed in the population of patients with metastatic breast cancer:

Primary efficacy objective:

To evaluate the efficacy of the treatment by assessment of:

  • clinical response rate (RR)
  • clinical benefit rate (CBR)

Secondary efficacy objectives:

To evaluate the efficacy of the treatment by assessment of:

  • time to progression (TTP)
  • overall survival (OS)

Pharmacokinetic objectives:

• to determine pharmacokinetic parameters for disulfiram and its active metabolites administered in combination with copper supplements in cancer patient population

Safety objectives:

• to describe safety profile of disulfiram administered in combination with copper supplements

Exploratory objectives:

Parallel analysis to assess (identify) potential candidate surrogate biomarkers of disulfiram efficacy, as well as identification (using proteomic, biochemical and molecular genetic studies) of potential predictive biomarkers of disulfiram sensitivity or resistance will be performed. Surrogate biomarker analysis will focus on in vivo ubiquitin-proteosomal system inhibition, cell cycle and DNA damage.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Inclusion criteria:

  1. Patients with stage IV breast cancer with metastases demonstrated by appropriate imaging techniques
  2. Histologically or cytologically confirmed tumor
  3. Age of 18 years or more
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2
  5. Patients have failed, untolerated or refused standard therapeutic modalities
  6. Not received systemic anticancer therapy or radiation or had major surgery in last 2 weeks
  7. Not currently participating in another study
  8. Anticipated survival of at least 2 months
  9. Baseline aspartate aminotransferase (AST) and alanine aminotransferase (ALT) not greater than 2.5 X upper institutional limit
  10. Serum copper within normal limits
  11. Serum ceruloplasmin > 17 mg/dL
  12. Able and willing to sign informed consent and to comply with study procedures
  13. Able to ingest oral medications
  14. No known allergy to disulfiram or copper
  15. Willing to refrain from ingestion of alcoholic beverages while on the study

Exclusion criteria:

  1. Participation in another clinical trial of a therapeutic drug during the past 14 days
  2. Addiction to alcohol or drugs
  3. Baseline AST or ALT greater than 2.5 X upper institutional limit
  4. Unable to ingest oral medications
  5. Unable to undergo CT/SPECT scanning because of inability to lie recumbent in the scanner
  6. Actively receiving cytotoxic cancer chemotherapy agents
  7. Anticipated survival of less than 2 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 negative pregnancy test before enrollment
  9. History of active liver disease, including chronic active hepatitis, viral hepatitis (hepatitis B, C and CMV), cholestatic jaundice of any etiology, toxic hepatitis, or cholestatic hepatitis or jaundice with bilirubin greater than 2.0 X upper institutional limit
  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 metronidazole, warfarin and/or theophylline medication, 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

Study Type

Interventional

Enrollment (Estimated)

150

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Czechia
      • Olomouc, Czechia, 77900
        • Recruiting
        • University Hospital Olomouc
        • Contact:
        • Contact:
        • Principal Investigator:
          • Bohuslav Melichar, MD., PhD.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Patients with stage IV breast cancer with metastases demonstrated by appropriate imaging techniques (computer tomography - CT, positron emission tomography - PET or PET/CT, MRI, ultrasound, etc.)
  2. Histologically or cytologically confirmed tumor
  3. Age of 18 years or more
  4. ECOG performance status of 0 - 2
  5. Patients have failed, untolerated or refused standard therapeutic modalities
  6. Not received systemic anticancer therapy or radiation or had major surgery in last 2 weeks
  7. Not currently participating in another study
  8. Anticipated survival of at least 2 months
  9. Baseline AST and ALT not greater than 2.5 X upper institutional limit
  10. Serum copper within normal limits
  11. Serum ceruloplasmin > 17 mg/dL
  12. Able and willing to sign informed consent and to comply with study procedures
  13. Able to ingest oral medications
  14. No known allergy to disulfiram or copper
  15. Willing to refrain from ingestion of alcoholic beverages while on the study

Exclusion Criteria:

  1. Participation in another clinical trial of a therapeutic drug during the past 14 days
  2. Addiction to alcohol or drugs
  3. Baseline AST or ALT greater than 2.5 X upper institutional limit
  4. Unable to ingest oral medications
  5. Unable to undergo CT/SPECT scanning because of inability to lie recumbent in the scanner
  6. Actively receiving cytotoxic cancer chemotherapy agents
  7. Anticipated survival of less than 2 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 negative pregnancy test before enrollment
  9. History of active liver disease, including chronic active hepatitis, viral hepatitis (hepatitis B, C and CMV), cholestatic jaundice of any etiology, toxic hepatitis, or cholestatic hepatitis or jaundice with bilirubin greater than 2.0 X upper institutional limit
  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 metronidazole, warfarin and/or theophylline medication, 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Disulfiram with copper

Patients will take one pill of disulfiram (Antabus) daily at a dose of 400 mg continually during the treatment phase (from day 0 till End of treatment Visit). In case of intolerance, lower dose up to 200 mg per day is allowed. Patients will take disulfiram after their evening meal.

Patients will avoid alcohol and other disulfiram-drug interactions will be considered.

Copper supplementation will be given separately from disulfiram; in the morning with patients´breakfast. Patients will take one pill of copper dietary supplement (for instance Copper Star, STARLIFE) corresponding to 2 mg of elementary copper.
Drug: Disulfiram

Patients will take one pill of disulfiram (Antabus) daily at a dose of 400 mg continually during the treatment phase (from day 0 till End of treatment Visit). In case of intolerance, lower dose up to 200 mg per day is allowed.

Copper supplementation will be given separately from disulfiram; in the morning with patients´breakfast. Patients will take one pill of copper dietary supplement (for instance Copper Star, STARLIFE) corresponding to 2 mg of elementary copper.

Other Names:
  • Copper

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical response rate (RR)
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
sum of complete and partial responses (CR+PR)
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Clinical benefit rate (CBR)
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
sum of complete, partial responses and stable diseases (CR+PR)CR+PR+SD)
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to progression (TTP)
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
time to progression (TTP) in months
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Overall survival (OS)
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
overall survival (OS) in months
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
The pharmacokinetic (PK) characteristics
Time Frame: Day 0 = at first administration of the drug
Cmax
Day 0 = at first administration of the drug
The pharmacokinetic (PK) characteristic - Area Under Curve (AUC)
Time Frame: Day 0 = at first administration of the drug
AUC - The area under the plasma concentration over the time
Day 0 = at first administration of the drug
The pharmacokinetic (PK) characteristic - T-max
Time Frame: Day 0 = at first administration of the drug
T-max - Time to reach maximum concentration
Day 0 = at first administration of the drug
The pharmacokinetic (PK) characteristic - T1/2
Time Frame: Day 0 = at first administration of the drug
T1/2 - Apparent terminal elimination half-life time
Day 0 = at first administration of the drug
The pharmacokinetic (PK) characteristic - λz
Time Frame: Day 0 = at first administration of the drug
λz (Lambda-z) - Individual estimate of the terminal elimination rate constant, calculated using log-linear regression of the terminal portions of the plasma concentration-versus-time curves
Day 0 = at first administration of the drug
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Number of participants with treatment-related adverse events analyzed as cumulative burden at every 6 months until study termination.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Institute of Molecular and Translational Medicine, Czech Republic

Collaborators

University Hospital Olomouc

Investigators

  • Study Chair: Marian Hajduch, MD., PhD., Palacky University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 29, 2017

Primary Completion (Estimated)

December 31, 2025

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

September 29, 2017

First Submitted That Met QC Criteria

October 25, 2017

First Posted (Actual)

October 27, 2017

Study Record Updates

Last Update Posted (Actual)

July 20, 2025

Last Update Submitted That Met QC Criteria

July 16, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2016-1-DSF-MBC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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