Metastatic breast cancer
Conditions
Interventions
Product Name: disulfiram
Pharmaceutical Form: Effervescent tablet
INN or Proposed INN: DISULFIRAM
CAS Number: 97-77-8
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number
Sponsors
Univerzita Palackého v Olomouci
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients with stage IV breast or IIIb-IV NSCLC with metastases demonstrated by appropriate imaging techniques (CT, 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, in tolerated or refused standard therapeutic modalities or for whom other systemic therapies are not an option 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 for patient without liver metastasis/not greater than 5.0 x upper institutional limit for patient with liver metastasis 10. Serum copper less than 40 micromol/l 11. Serum ceruloplasmin > 17 mg/dL but not greater than 2.5 x upper institutional limit 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 90 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
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 for patient without liver metastasis/not greater than 5.0 x upper institutional limit for patient with liver metastasis 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 had a positive pregnancy test before enrollment; the pregnancy test was used more than 7 days before screening visit 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 iron overload syndron, hemochromatosis or family member with hemochromatosis 12. Need for metronidazole, warfarin and/or theophylline medication, the metabolism of which is likely influenced by disulfiram 13. Pregnant women and nursing 14. Patients who are taking medications metabolized by cytochrome P450 2E1, including chlorzoxazone or halothane and its derivatives
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: Secondary efficacy objectives: To evaluate the efficacy of the treatment by assessment of: 1) to evaluate time to progression (TTP) 2) to evaluate overal survival (OS) Safety objective: to describe safety profile of disulfiram administered in combination with copper supplements Pharmacokinetic objectives: to determine pharmacokinetic parameters for disulfiram with its active metabolites administered in combination with supplements with copper in patient with MBC. Exploratory objectives: Parallel analysis to assess (identify) potential candidate surrogate biomarkers of disulfiram efficacy, as well as identification of potential predictive biomarkers of disulfiram sensitivity or resistence will be performed. Surrogate biomarker analysis will focus on in vivo UPS inhibition, cell cycle and DNA damage.;Primary end point(s): Efficacy Outcome Measures Primary: • effect of treatment with disulfiram and copper on clinical response rate (RR, percentage of patients whose cancer shrinks; termed a partial response, PR; or disappears after treatment; termed a complete response, CR; RR=PR+CR) • effect of treatment with disulfiram and copper on clinical benefit rate (CBR=CR+PR+SD). RR and CBR will be evaluated using RECIST version 1.1 criteria.;Timepoint(s) of evaluation of this end point: RR and CBR will be evaluated using RECIST version 1.1 criteria.;Main Objective: Primary efficacy objectives: to evaluate the efficacy of the treatment by assessment of 1)clinical response rate (RR), 2)clinical benefit rate (CBR). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy Outcome Measures: Secondary: • Time to progression (TTP) • Overall survival (OS) Patients will be evaluated with CT/SPECT scan every 12 weeks (3 months). The extent of tumor control less than 10% after 3 months (at the second CT scan) is regarded not clinically relevant.;Timepoint(s) of evaluation of this end point: Patients will be evaluated with CT/SPECT scan every 12 weeks (3 months). The extent of tumor control less than 10% after 3 months (at the second CT scan) is regarded not clinically relevant. | — |
Countries
Czech Republic
Contacts
Public Contactdoc. MUDr. Regina Demlová, Ph.D.
Masarykova univerzita
Outcome results
None listed