Phase II Trial of Disulfiram With Copper in Metastatic Breast Cancer

NCT03323346 | Recruiting Phase 2

• 1 other identifier: 2016-1-DSF-MBC
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Breast Neoplasm Female; Metastatic Breast Cancer

Keywords

metastatic breast cancer; disulfiram; cooper

Outcome Measures

Primary Outcomes (2)

• Clinical response rate (RR)

  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)

  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 Outcomes (8)

• Time to progression (TTP)

  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)

  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

  Day 0 = at first administration of the drug

• The pharmacokinetic (PK) characteristic - Area Under Curve (AUC)

  Day 0 = at first administration of the drug

• The pharmacokinetic (PK) characteristic - T-max

  Day 0 = at first administration of the drug

Study Arms (1)

Disulfiram with copper

EXPERIMENTAL

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

Interventions

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.

Also known as: Copper

Disulfiram with copper

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The Institute of Molecular and Translational Medicine, Czech Republic: lead
• University Hospital Olomouc: collaborator

Study Sites (1)

University Hospital Olomouc

Olomouc, 77900, Czechia

RECRUITING

Related Publications (11)

• Askgaard G, Friis S, Hallas J, Thygesen LC, Pottegard A. Use of disulfiram and risk of cancer: a population-based case-control study. Eur J Cancer Prev. 2014 May;23(3):225-32. doi: 10.1097/CEJ.0b013e3283647466.

  PMID: 23863824 BACKGROUND

• Wickstrom M, Danielsson K, Rickardson L, Gullbo J, Nygren P, Isaksson A, Larsson R, Lovborg H. Pharmacological profiling of disulfiram using human tumor cell lines and human tumor cells from patients. Biochem Pharmacol. 2007 Jan 1;73(1):25-33. doi: 10.1016/j.bcp.2006.08.016. Epub 2006 Aug 26.

  PMID: 17026967 BACKGROUND

• Schweizer MT, Lin J, Blackford A, Bardia A, King S, Armstrong AJ, Rudek MA, Yegnasubramanian S, Carducci MA. Pharmacodynamic study of disulfiram in men with non-metastatic recurrent prostate cancer. Prostate Cancer Prostatic Dis. 2013 Dec;16(4):357-61. doi: 10.1038/pcan.2013.28. Epub 2013 Aug 20.

  PMID: 23958896 BACKGROUND

• Brar SS, Grigg C, Wilson KS, Holder WD Jr, Dreau D, Austin C, Foster M, Ghio AJ, Whorton AR, Stowell GW, Whittall LB, Whittle RR, White DP, Kennedy TP. Disulfiram inhibits activating transcription factor/cyclic AMP-responsive element binding protein and human melanoma growth in a metal-dependent manner in vitro, in mice and in a patient with metastatic disease. Mol Cancer Ther. 2004 Sep;3(9):1049-60.

  PMID: 15367699 BACKGROUND

• Lewison EF. Spontaneous regression of breast cancer. Prog Clin Biol Res. 1977;12:47-53. No abstract available.

  PMID: 918117 BACKGROUND

• Lin J, Haffner MC, Zhang Y, Lee BH, Brennen WN, Britton J, Kachhap SK, Shim JS, Liu JO, Nelson WG, Yegnasubramanian S, Carducci MA. Disulfiram is a DNA demethylating agent and inhibits prostate cancer cell growth. Prostate. 2011 Mar 1;71(4):333-43. doi: 10.1002/pros.21247. Epub 2010 Aug 31.

  PMID: 20809552 BACKGROUND

• Robinson TJ, Pai M, Liu JC, Vizeacoumar F, Sun T, Egan SE, Datti A, Huang J, Zacksenhaus E. High-throughput screen identifies disulfiram as a potential therapeutic for triple-negative breast cancer cells: interaction with IQ motif-containing factors. Cell Cycle. 2013 Sep 15;12(18):3013-24. doi: 10.4161/cc.26063. Epub 2013 Aug 12.

  PMID: 23974104 BACKGROUND

• Cvek B, Milacic V, Taraba J, Dou QP. Ni(II), Cu(II), and Zn(II) diethyldithiocarbamate complexes show various activities against the proteasome in breast cancer cells. J Med Chem. 2008 Oct 23;51(20):6256-8. doi: 10.1021/jm8007807. Epub 2008 Sep 25.

  PMID: 18816109 BACKGROUND

• Chen D, Cui QC, Yang H, Dou QP. Disulfiram, a clinically used anti-alcoholism drug and copper-binding agent, induces apoptotic cell death in breast cancer cultures and xenografts via inhibition of the proteasome activity. Cancer Res. 2006 Nov 1;66(21):10425-33. doi: 10.1158/0008-5472.CAN-06-2126.

  PMID: 17079463 BACKGROUND

• Cvek B. Nonprofit drugs as the salvation of the world's healthcare systems: the case of Antabuse (disulfiram). Drug Discov Today. 2012 May;17(9-10):409-12. doi: 10.1016/j.drudis.2011.12.010. Epub 2011 Dec 16.

  PMID: 22192884 BACKGROUND

• Suh JJ, Pettinati HM, Kampman KM, O'Brien CP. The status of disulfiram: a half of a century later. J Clin Psychopharmacol. 2006 Jun;26(3):290-302. doi: 10.1097/01.jcp.0000222512.25649.08.

  PMID: 16702894 BACKGROUND

Related Links

• The trial status on sponsor's website.

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Disulfiram; Copper

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Ditiocarb; Thiocarbamates; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Disulfides; Sulfides; Sulfur Compounds; Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals

Study Officials

• Marian Hajduch, MD., PhD.

  Palacky University

  STUDY CHAIR

Central Study Contacts

Marian Hajduch, MD., PhD.

CONTACT

+420 585632111; marian.hajduch@upol.cz

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2017
• First Posted: October 27, 2017
• Study Start: September 29, 2017
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: July 20, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (1)