Phase II Trial of Disulfiram With Copper in Metastatic Breast Cancer (DISC)
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT03323346 |
|
Recruitment Status :
Recruiting
First Posted : October 27, 2017
Last Update Posted : March 8, 2023
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Breast Neoplasm Female Metastatic Breast Cancer | Drug: Disulfiram | Phase 2 |
Inclusion criteria:
- Patients with stage IV breast cancer with metastases demonstrated by appropriate imaging techniques
- Histologically or cytologically confirmed tumor
- Age of 18 years or more
- Eastern Cooperative Oncology Group (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 aspartate aminotransferase (AST) and alanine aminotransferase (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
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 150 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Phase II Open Labeled Trial of Disulfiram With Copper in Metastatic Breast Cancer |
| Actual Study Start Date : | September 29, 2017 |
| Estimated Primary Completion Date : | December 31, 2023 |
| Estimated Study Completion Date : | December 31, 2023 |
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Disulfiram with copper
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
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. Other Name: Copper |
- Clinical response rate (RR) [ Time Frame: 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 ]sum of complete and partial responses (CR+PR)
- Clinical benefit rate (CBR) [ Time Frame: 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 ]sum of complete, partial responses and stable diseases (CR+PR)CR+PR+SD)
- Time to progression (TTP) [ Time Frame: 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 ]time to progression (TTP) in months
- Overall survival (OS) [ Time Frame: 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) in months
- The pharmacokinetic (PK) characteristics [ Time Frame: Day 0 = at first administration of the drug ]Cmax
- The pharmacokinetic (PK) characteristic - Area Under Curve (AUC) [ Time Frame: Day 0 = at first administration of the drug ]AUC - The area under the plasma concentration over the time
- The pharmacokinetic (PK) characteristic - T-max [ Time Frame: Day 0 = at first administration of the drug ]T-max - Time to reach maximum concentration
- The pharmacokinetic (PK) characteristic - T1/2 [ Time Frame: Day 0 = at first administration of the drug ]T1/2 - Apparent terminal elimination half-life time
- The pharmacokinetic (PK) characteristic - λz [ Time Frame: Day 0 = at first administration of the drug ]λz (Lambda-z) - Individual estimate of the terminal elimination rate constant, calculated using log-linear regression of the terminal portions of the plasma concentration-versus-time curves
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 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 ]Number of participants with treatment-related adverse events analyzed as cumulative burden at every 6 months until study termination.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03323346
| Contact: Marian Hajduch, MD., PhD. | +420 585632111 | marian.hajduch@upol.cz |
| Czechia | |
| University Hospital Olomouc | Recruiting |
| Olomouc, Czechia, 77900 | |
| Contact: Bohuslav Melichar, MD., PhD. +420588444295 bohuslav.melichar@fnol.cz | |
| Contact: Lucie Stejskalova, MSc. +420588444295 lucie.stejskalova@fnol.cz | |
| Principal Investigator: Bohuslav Melichar, MD., PhD. | |
| Study Chair: | Marian Hajduch, MD., PhD. | Palacky University |
Publications:
| Responsible Party: | The Institute of Molecular and Translational Medicine, Czech Republic |
| ClinicalTrials.gov Identifier: | NCT03323346 |
| Other Study ID Numbers: |
2016-1-DSF-MBC |
| First Posted: | October 27, 2017 Key Record Dates |
| Last Update Posted: | March 8, 2023 |
| Last Verified: | March 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
|
metastatic breast cancer disulfiram cooper |
|
Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases |
Disulfiram Alcohol Deterrents Acetaldehyde Dehydrogenase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |