Clinical trial · Interventional
Phase II Trial of Disulfiram With Copper in Metastatic Breast Cancer
Phase II Open Labeled Trial of Disulfiram With Copper in Metastatic Breast Cancer
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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
Conditions (2)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Breast Neoplasm Female | Breast Neoplasm | PROBABILISTIC | 0.70 |
| Metastatic Breast Cancer | Malignant Breast Neoplasm | CURATED_BROADER | 0.78 |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Disulfiram | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Disulfiram with copper
- description
- 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.
- interventionNames
- Drug: Disulfiram
Primary outcomes (2)
- measure
- Clinical response rate (RR)
- timeFrame
- 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
- description
- sum of complete and partial responses (CR+PR)
Eligibility
Eligibility (as posted)
- Sex
- Female
- Minimum age
- 18 Years
Show eligibility criteria text
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
References
Publications (11)
- BACKGROUNDAskgaard 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
- BACKGROUNDWickstrom 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
- BACKGROUNDSchweizer 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
- BACKGROUNDBrar 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
- BACKGROUNDLewison EF. Spontaneous regression of breast cancer. Prog Clin Biol Res. 1977;12:47-53. No abstract available. PMID 918117
- BACKGROUNDLin 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
- BACKGROUNDRobinson 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.