Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Paclitaxel

Albumin-Bound Paclitaxel

Capecitabine

Vinorelbine

Interleukin 1 Receptor Antagonist Protein

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Patients will undergo a 2-week run-in treatment of daily anakinra alone. This will be followed by daily anakinra (100 mg SC) plus the physician's chemotherapy ( TPC) choice of standard of care (SOC) for a maximum of 6 months.TPC choice includes nab paclitaxel (100 mg/m\^2 Intravenous on day 1,8 \&15 of a 28 day cycle), or capecitabine (1000mg/m\^2 per oral; BID choice: 14 days on, 7 days off OR 7 days on, 7 days off of a 21 day cycle), or eribulin (1.4 mg/m\^2 intravenous on day 1 \& 8 of a 21 day cycle), or vinorelbine (25mg/m\^2 on day 1,8,15 of a 28 day cycle). After 6 months, patients may continue their SOC treatment alone until disease progression or intolerable toxicity.

Anakinra plus Standard of Care

Joyce O'Shaughnessy, MD

To determine the safety of administering anakinra plus the physician's chemotherapy choice (TPC) of nab paclitaxel, capecitabine, eribulin, or vinorelbine in patients with metastatic breast cancer (MBC), as well as determining blood immune cell transcriptional signatures in patients who undergo IL-1 receptor blockade.

In an attempt to reverse the immune suppressive microenvironment and to enhance chemotherapy effectiveness, decrease tumor metagenicity and decrease IL-1-induced fatigue, metastatic breast cancer (MBC) patients will be treated with chemotherapy plus anakinra. This is a pilot safety, single arm, open label trial. The objective is to determine the safety of anakinra plus the physician's chemotherapy choice (TPC) of nab paclitaxel, capecitabine, eribulin, or vinorelbine in patients with MBC and to define an anakinra-induced anti-IL-1 whole blood transcriptional profile.

Safety and Blood Immune Cell Study of Anakinra Plus Physician's Chemotherapy Choice in Metastatic Breast Cancer Patients

Pilot Safety and Blood Immune Cell Transcriptional Profiling Study of Anakinra Plus the Physician's Chemotherapy Choice in Metastatic Breast Cancer Patients

Patients will receive anakinra plus the physicians chemotherapy choice of nab paclitaxel, or capecitabine, or eribulin, or vinorelbine for metastatic breast cancer. Adverse events will be recorded throughout the trial, and regardless of the severity will be followed up by investigator until resolution is satisfactory. All adverse events and toxicities will be recorded and assessed for 30 days following the last dose of anakinra at a maximum of 6 months. Grading will be done using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.

Objective response rate, clinical benefit rate and progression-free survival in patients will be determined using radiological assessment of tumors (CT/MRI/X-ray/PET), clinical and functional evaluation of patients with 95% confidence intervals. Whole blood transcriptional profiling will be performed to determine a gene expression signature that is induced by IL-1 receptor blockade by anakinra. The gene expression signatures from baseline will be compared to those signatures obtained after the 2-week run-in treatment with anakinra alone. During the treatment, complete blood count with differential/platelet count and complete metabolic profiling will be done to identify any baseline changes.

Baylor Research Institute

Alcohol Deterrents

Micronutrients

Anti-Infective Agents

Central Nervous System Depressants

Mineral

Cisplatin

Disulfiram

Copper

Trace Elements

Ethanol

Enzyme Inhibitors

Copper Supplement

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.

Vinorelbin

Michal Mego, Prof

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.

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.

Vinorelbine, Cisplatin, Disulfiram and Copper in CTC_EMT Positive Refractory Metastatic Breast Cancer.

Phase II Study of Vinorelbine, Cisplatin, Disulfiram and Copper in CTC_EMT Positive Refractory Metastatic Breast Cancer.

Time from first administration of the study drug till progression

Time from first administration of the study drug till death

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Safety and Blood Immune Cell Study of Anakinra Plus Physician's Chemotherapy Choice in Metastatic Breast Cancer Patients	NCT01802970	Metastatic Brea...	Anakinra plus S...	18 Years - 80 Years	Baylor Research Institute
Vinorelbine, Cisplatin, Disulfiram and Copper in CTC_EMT Positive Refractory Metastatic Breast Cancer.	NCT04265274	Metastatic Brea...	Disulfiram Vinorelbin Cisplatin Copper	18 Years -	National Cancer Institute, Slovakia

Spots Global Cancer Trial Database for vinorelbin

Every month we try and update this database with for vinorelbin cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for vinorelbin

Every month we try and update this database with for vinorelbin cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for vinorelbin cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.