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Completed

NCT Number: NCT03323346

Phase II 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.

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Key information

Conditions

Breast Neoplasm Female Breast Diseases Breast Neoplasms Metastatic Breast Cancer Neoplasms Neoplasms by Site Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 2

Primary location

University Hospital Olomouc

Olomouc, 77900, Czechia

About this study

Inclusion criteria

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

Exclusion criteria

  • Participation in another clinical trial of a therapeutic drug during the past 14 days
  • Addiction to alcohol or drugs
  • Baseline AST or ALT greater than 2.5 X upper institutional limit
  • Unable to ingest oral medications
  • Unable to undergo CT/SPECT scanning because of inability to lie recumbent in the scanner
  • Actively receiving cytotoxic cancer chemotherapy agents
  • Anticipated survival of less than 2 months
  • 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
  • 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
  • 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 metronidazole, warfarin and/or theophylline medication, 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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.)
  • Histologically or cytologically confirmed tumor
  • Age of 18 years or more
  • ECOG performance status of 0 - 2
  • Patients have failed, untolerated or refused standard therapeutic modalities
  • Not received systemic anticancer therapy or radiation or had major surgery in last 2 weeks
  • Not currently participating in another study
  • Anticipated survival of at least 2 months
  • Baseline AST and ALT not greater than 2.5 X upper institutional limit
  • Serum copper within normal limits
  • Serum ceruloplasmin > 17 mg/dL
  • Able and willing to sign informed consent and to comply with study procedures
  • Able to ingest oral medications
  • No known allergy to disulfiram or copper
  • Willing to refrain from ingestion of alcoholic beverages while on the study

Exclusion criteria

  • Participation in another clinical trial of a therapeutic drug during the past 14 days
  • Addiction to alcohol or drugs
  • Baseline AST or ALT greater than 2.5 X upper institutional limit
  • Unable to ingest oral medications
  • Unable to undergo CT/SPECT scanning because of inability to lie recumbent in the scanner
  • Actively receiving cytotoxic cancer chemotherapy agents
  • Anticipated survival of less than 2 months
  • 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
  • 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
  • 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 metronidazole, warfarin and/or theophylline medication, 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

Treatment and study plan

Disulfiram

Drug

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

Primary outcomes

  1. 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)

  2. 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)

Secondary outcomes

  1. 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

  2. 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

  3. The pharmacokinetic (PK) characteristics

    Time frame: Day 0 = at first administration of the drug

    Cmax

  4. 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

  5. The pharmacokinetic (PK) characteristic - T-max

    Time frame: Day 0 = at first administration of the drug

    T-max - Time to reach maximum concentration

  6. The pharmacokinetic (PK) characteristic - T1/2

    Time frame: Day 0 = at first administration of the drug

    T1/2 - Apparent terminal elimination half-life time

  7. 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

  8. 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.

Sponsors and collaborators

Lead sponsor

The Institute of Molecular and Translational Medicine, Czech Republic

Other

Collaborators

  • University Hospital Olomouc

Registry information

Official study title

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

Acronym: DISC

Important dates

Study start
2017
Primary completion
2025
Study completion
2025
First posted
Oct 27, 2017
Registry last updated
Jun 26, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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