Vinorelbine, Cisplatin, Disulfiram and Copper in CTC_EMT Positive Refractory Metastatic Breast Cancer.
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|ClinicalTrials.gov Identifier: NCT04265274|
Recruitment Status : Recruiting
First Posted : February 11, 2020
Last Update Posted : February 11, 2020
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Breast Cancer||Drug: Disulfiram Drug: Vinorelbin Drug: Cisplatin Drug: Copper||Phase 2|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||28 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Study of Vinorelbine, Cisplatin, Disulfiram and Copper in CTC_EMT Positive Refractory Metastatic Breast Cancer.|
|Actual Study Start Date :||January 1, 2020|
|Estimated Primary Completion Date :||January 1, 2022|
|Estimated Study Completion Date :||January 1, 2023|
Experimental: Disulfiram, vinorelbin, cisplatin, copper
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.
dosing 400mg daily
Other Name: Antabus
25mg/m2 day 1 and 8,
Other Name: Navelbine
75mg/m2 day 1
2 mg of elementary Copper daily
- Objective response rates [ Time Frame: 6 months ]Response rate according to RECIST
- Progression-free survival [ Time Frame: 12 months ]Time from first administration of the study drug till progression
- overall survival [ Time Frame: 12 months ]Time from first administration of the study drug till death
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): NCT04265274
|Contact: Daniela Svetlovska, Dr||+421-2-59378 ext firstname.lastname@example.org|
|Contact: Michal Mego, Prof||+421-2-59378 ext email@example.com|
|National Cancer Institute||Recruiting|
|Bratislava, Slovakia, 83310|
|Contact: Michal Mego, Assoc. Prof +421259378 ext 366 firstname.lastname@example.org|
|Contact: Daniela Svetlovska, Dr +421259378 ext 592 email@example.com|
|Principal Investigator: Michal Mego, Prof|
|Study Chair:||Michal Mego, Prof||National Cancer Institute, Slovakia|