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.
• 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