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

  • STATUS
    Recruiting
  • days left to enroll
    28
  • participants needed
    150
  • sponsor
    The Institute of Molecular and Translational Medicine, Czech Republic
Updated on 4 October 2022
cancer
breast cancer
major surgery
metastasis
biomarker analysis
cancer treatment
disulfiram
copper
dna damage
serum copper

Summary

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.

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

Details
Condition Breast Neoplasm Female, Metastatic Breast Cancer
Treatment Disulfiram
Clinical Study IdentifierNCT03323346
SponsorThe Institute of Molecular and Translational Medicine, Czech Republic
Last Modified on4 October 2022

Eligibility

Yes No Not Sure

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
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