Metastatic Breast CancerPhase 2NCT04265274
Vinorelbine, Cisplatin, Disulfiram and Copper in CTC_EMT Positive Refractory Metastatic Breast Cancer.
A Phase 2 study testing Disulfiram, Vinorelbin and Cisplatin in people with Metastatic Breast Cancer, run by National Cancer Institute, Slovakia at 1 site in Slovakia.
Trial summary
This is a proof-of-concept study to define efficacy of vinorelbine, cisplatin, disulfiram and copper in CTC_EMT positive refractory metastatic hormone receptor positive, HER2 negative breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- Disulfiram, Vinorelbin and Cisplatin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteSlovakia
- Study dates
- 1 Jan 2020to 1 Jan 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Patients who have received any of the following treatments within the specified period before study treatment start: chemotherapy, radiation, trastuzumab or hormonal therapy within three weeks, any investigational drug within four weeks, radiation therapy encompassing > 30% of marrow.
- Addiction to alcohol or drugs.
- Need for metronidazole, warfarin and/or theophylline medication, the metabolism of which is likely influenced by disulfiram and copper, see Table 4.
- Patients who are taking medications metabolized by cytochrome P450 2E1, including chlorzoxazone or halothane and its derivatives, see Table 4.
- Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen.
- Patients with brain or subdural metastases are not eligible, unless they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study. Any signs (e.g., radiologic) and/or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment; radiographic stability should be determined by comparing a contrast-enhanced computed tomography or magnetic resonance imaging brain scan performed during screening to a prior scan performed at least 4 weeks earlier.
Show all 15Show fewer
- Patients with meningeal carcinomatosis.
- Women who are pregnant or breast-feeding; women of childbearing potential with either a positive pregnancy test at screening or no pregnancy test; women of childbearing potential unless (1) surgically sterile or (2) using adequate measures of contraception in the opinion of the Investigator. Perimenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
- Severe/uncontrolled intercurrent illness/infection.
- Patients with organ allografts requiring immunosuppression.
- Patients with known positive HIV status.
- Hemochromatosis.
- Patients who have had a prior malignancy, other than previous breast cancer, carcinoma in situ of the cervix, or non-melanoma skin cancer, unless the prior malignancy was diagnosed and definitively treated >= 5 years previously with no subsequent evidence of recurrence.
- Patients with pre-existing neuropathy > Grade 2.
- Patients with other significant disease or disorders that, in the Investigator's opinion, would exclude the patient from the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Study of Vinorelbine, Cisplatin, Disulfiram and Copper in CTC_EMT Positive Refractory Metastatic Breast Cancer.
This is a proof-of-concept study to define efficacy of vinorelbine, cisplatin, disulfiram and copper in CTC_EMT positive refractory metastatic hormone receptor positive, HER2 negative breast cancer.
Read the detailed description
Despite advances in breast cancer prevention, diagnosis, and therapy, 5-10% of patients with breast cancer have metastatic disease at initial presentation, and approximately 30% of patients with breast cancer develop metastatic disease during the course of disease. Metastatic cascade is a multistep process that enables the migration of tumor cells from the primary site to a distant location, where they can potentially establish a new cancer growth. To execute the metastatic cascade, epithelial cancer cells must detach from the primary tumor, pass through the peripheral circulation, extravasate at the distant site and create a new tumor.
Experimental and clinical data suggest a close relationship between activation of EMT program and generation of CTCs. EMT is associated with a set of molecular changes in epithelial cancer cells that results in increased motility and the induction of proteases that are involved in degradation of the extracellular matrix facilitating thus invasion and intravasation into the bloodstream. EMT has also been linked to the stem cell phenotype and resistance to apoptotic signals, facilitating EMT-derived CTCs to survive in foreign environments. Cancer stem cell phenotype is closely related to ALDH expression. Several studies showed that CTCs with EMT phenotype is associated with inferior outcome in primary as well as in metastatic setting.
In a biomarker study in primary breast cancer, CTC_EMT were detected in 77 (18.0%) of patients. Patients without detectable CTC_EMT in the peripheral blood had significantly superior DFS compared to patients with detectable CTC_EMT (HR = 0.42, 95%CI 0.22 - 0.78, p = 0.0003). Prognostic value of CTC_EMT was demonstrated in all subgroups of patients, most pronounced in hormone receptor positive, HER2 negative subgroup. In multivariate analysis, presence of CTC_EMT, axillary nodal involvement and hormone receptor status were independently associated with DFS. Presence of CTC_EMT could lead to better identification of patients with increased risk of recurrence, especially in hormone receptor positive, HER-2 negative primary breast cancer patients.
Disulfiram (DSF) in combination with copper (Cu) has been reported to override drug resistance in cancer cells, and DSF combined with chemotherapy based on the microtubule inhibitor vinorelbine appears to prolong survival in non-small cell lung cancer patients.
Based on aforementioned data, it is suggested that there is strong rationale to inhibit ALDH in MBC. Inactivation of ALDH by disulfiram/copper will be lead to increase of objective response rate in patients with refractory MBC.
- Conditions
- Metastatic Breast Cancer
- Being tested
- Disulfiram, Vinorelbin, Cisplatin, Copper
- Keywords
- metastatic breast cancer, vinorelbin, cisplatin, disulfiram
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DisulfiramDrug
Also called Antabus
dosing 400mg daily
VinorelbinDrug
Also called Navelbine
25mg/m2 day 1 and 8,
CisplatinDrug
75mg/m2 day 1
CopperDrug
2 mg of elementary Copper daily
| Study group | Role | What they receive |
|---|---|---|
| Disulfiram, vinorelbin, cisplatin, copper | Experimental | Vinorelbine 25mg/m2 day 1 and 8, Cisplatin 75mg/m2 day 1, every 3 weeks, Disulifiram um 400mg daily and 2 mg of elementary Copper daily, continuously. Receives: Drug: Disulfiram; Drug: Vinorelbin; Drug: Cisplatin; Drug: Copper |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rates
Response rate according to RECIST
Measured: 6 months
Secondary outcomes (2)
Progression-free survival
Time from first administration of the study drug till progression
Measured: 12 months
overall survival
Time from first administration of the study drug till death
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2020
- Study start1 Jan 2020
- Primary completion1 Jan 2022
- Study completion1 Jan 2023
Why it stopped: Poor acrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute, Slovakia
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Michal Mego, Prof, Study chair, National Cancer Institute, Slovakia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04265274
- Sponsor's protocol ID
- BREAST-SK-001
- Status last verified
- Oct 2023
- First submitted
- 5 Feb 2020
- Last updated
- 6 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Vinorelbine, Cisplatin, Disulfiram and Copper in CTC_EMT Positive Refractory Metastatic Breast Cancer.
- ClinicalTrials.gov ID
- NCT04265274
- Acronym / sponsor ID
- BREAST-SK-001
- Conditions
- Metastatic Breast Cancer
- Keywords
- metastatic breast cancer, vinorelbin, cisplatin, disulfiram
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Poor acrual
- Enrolment
- 0 participants (actual)
- Lead sponsor
- National Cancer Institute, SlovakiaOther government
- Study start
- 1 Jan 2020 (actual)
- Primary completion
- 1 Jan 2022 (actual)
- Study completion
- 1 Jan 2023 (actual)
- First posted
- 11 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a proof-of-concept study to define efficacy of vinorelbine, cisplatin, disulfiram and copper in CTC_EMT positive refractory metastatic hormone receptor positive, HER2 negative breast cancer.
Detailed description
Despite advances in breast cancer prevention, diagnosis, and therapy, 5-10% of patients with breast cancer have metastatic disease at initial presentation, and approximately 30% of patients with breast cancer develop metastatic disease during the course of disease. Metastatic cascade is a multistep process that enables the migration of tumor cells from the primary site to a distant location, where they can potentially establish a new cancer growth. To execute the metastatic cascade, epithelial cancer cells must detach from the primary tumor, pass through the peripheral circulation, extravasate at the distant site and create a new tumor.
Experimental and clinical data suggest a close relationship between activation of EMT program and generation of CTCs. EMT is associated with a set of molecular changes in epithelial cancer cells that results in increased motility and the induction of proteases that are involved in degradation of the extracellular matrix facilitating thus invasion and intravasation into the bloodstream. EMT has also been linked to the stem cell phenotype and resistance to apoptotic signals, facilitating EMT-derived CTCs to survive in foreign environments. Cancer stem cell phenotype is closely related to ALDH expression. Several studies showed that CTCs with EMT phenotype is associated with inferior outcome in primary as well as in metastatic setting.
In a biomarker study in primary breast cancer, CTC_EMT were detected in 77 (18.0%) of patients. Patients without detectable CTC_EMT in the peripheral blood had significantly superior DFS compared to patients with detectable CTC_EMT (HR = 0.42, 95%CI 0.22 - 0.78, p = 0.0003). Prognostic value of CTC_EMT was demonstrated in all subgroups of patients, most pronounced in hormone receptor positive, HER2 negative subgroup. In multivariate analysis, presence of CTC_EMT, axillary nodal involvement and hormone receptor status were independently associated with DFS. Presence of CTC_EMT could lead to better identification of patients with increased risk of recurrence, especially in hormone receptor positive, HER-2 negative primary breast cancer patients.
Disulfiram (DSF) in combination with copper (Cu) has been reported to override drug resistance in cancer cells, and DSF combined with chemotherapy based on the microtubule inhibitor vinorelbine appears to prolong survival in non-small cell lung cancer patients.
Based on aforementioned data, it is suggested that there is strong rationale to inhibit ALDH in MBC. Inactivation of ALDH by disulfiram/copper will be lead to increase of objective response rate in patients with refractory MBC.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Disulfiram, vinorelbin, cisplatin, copper | Experimental | Drug: Disulfiram, Drug: Vinorelbin, Drug: Cisplatin, Drug: CopperVinorelbine 25mg/m2 day 1 and 8, Cisplatin 75mg/m2 day 1, every 3 weeks, Disulifiram um 400mg daily and 2 mg of elementary Copper daily, continuously. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (15 listed)
- Patients who have received any of the following treatments within the specified period before study treatment start: chemotherapy, radiation, trastuzumab or hormonal therapy within three weeks, any investigational drug within four weeks, radiation therapy encompassing > 30% of marrow.
- Addiction to alcohol or drugs.
- Need for metronidazole, warfarin and/or theophylline medication, the metabolism of which is likely influenced by disulfiram and copper, see Table 4.
- Patients who are taking medications metabolized by cytochrome P450 2E1, including chlorzoxazone or halothane and its derivatives, see Table 4.
- Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DisulfiramAlso: Antabusdosing 400mg daily | Drug | Disulfiram, vinorelbin, cisplatin, copper |
| VinorelbinAlso: Navelbine25mg/m2 day 1 and 8, | Drug | Disulfiram, vinorelbin, cisplatin, copper |
| Cisplatin75mg/m2 day 1 | Drug | Disulfiram, vinorelbin, cisplatin, copper |
| Copper2 mg of elementary Copper daily | Drug | Disulfiram, vinorelbin, cisplatin, copper |
Primary outcome
Objective response rates
Time frame: 6 months
Response rate according to RECIST
2 secondary outcomes
Progression-free survival
Time frame: 12 months
overall survival
Time frame: 12 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2023.
- Individual participant dataSharing planned: No
Related trials for Metastatic Breast Cancer
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruiting
Augmented-Reality ICG Fluorescence Second-Look for Residual Nodal Disease After Axillary Dissection in Breast Cancer
Breast Cancer, Breast Neoplasms
RecruitingPhase 2
BrAin Metastasis in tripLe Negateive Breast Cancer: IvoneScimab and Trop2 ADC
Triple-Negative Breast Cancer (TNBC), Brain Metastases
RecruitingPhase 1/2
A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer
Metastatic Breast Cancer
RecruitingObservational study
Collection of CSF Samples From Participants With Metastatic Triple Negative Breast Cancer (TNBC) and HER2+ Breast Cancer With no Prior History Nor Active Radiographically Detectable Brain Metastases
Breast Cancer, Breast Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michal Mego, Prof study chair
National Cancer Institute, Slovakia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Disulfiram, Vinorelbin and Cisplatin in people with Metastatic Breast Cancer, run by National Cancer Institute, Slovakia at 1 site in Slovakia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 6 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Slovakia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rates (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2023.