Study to evaluate effectiveness and toxicity of combination vinorelbine, cisplatin and disulfiram and copper for treatment of breast cancer with present circulating tumor cells, who did not respond to previous therapy.
- Conditions
- breast cancerMedDRA version: 20.0Level: PTClassification code 10006187Term: Breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-001957-16-SK
- Lead Sponsor
- árodný onkologický ústav
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Female
- Target Recruitment
- 0
1)Female patients with histologically confirmed carcinoma of the breast.
2)CTC_EMT positivity in the peripheral blood.
3)Patients with locally recurrent or metastatic, hormone receptor positive, HER2 negative disease HER2 negative who have received at least two (and not more than five) prior chemotherapeutic regimens for breast cancer, at least two of which were administered for treatment of locally recurrent and/or metastatic disease.
4)Prior therapy must be documented by the following criteria prior to entry onto study:
-Regimens must have included an anthracycline (eg., doxorubicin, epirubicin) and a taxane (e.g., paclitaxel, docetaxel) in any combination or order. Treatment with any of these agents is not required if they are contraindicated for a certain patient.
-One or two of these regimens may have been administered as adjuvant and/or neoadjuvant therapy, but at least 2 must have been given for relapsed or metastatic disease.
-Patients must have proved refractory to the most recent chemotherapy, documented by progression on or within six (6) months of therapy.
5)Patients may have additionally been treated with anti-hormonal therapy.
6)Resolution of all chemotherapy or radiation-related toxicities to Grade 1 severity or lower, except for stable sensory neuropathy <= Grade 2 and alopecia.
7)Age >= 18 years.
8)Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2.
9)Life expectancy of >= 3 months.
10)Adequate renal function as evidenced by calculated creatinine clearance >= 40 mL/min per the Cockcroft and Gault formula.
11)Adequate bone marrow function as evidenced by absolute neutrophil count (ANC) >= 1.5 x 10^9/L, hemoglobin >= 9.0 g/dL (a hemoglobin <10.0 g/dL is acceptable if it is corrected by growth factor or transfusion), and platelet count >= 100 x 10^9/L.
12)Adequate liver function as evidenced by bilirubin <= 1.5 times the upper limits of normal (ULN) and alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) <= 3 x ULN (in the case of liver metastases <= 5 x ULN), unless there are bone metastases, in which case liver specific alkaline phosphatase must be separated from the total and used to assess the liver function instead of the total alkaline phosphatase. In case alkaline phosphatase is >3 x ULN (in absence of liver metastases) or > 5 x ULN (in presence of liver metastases) AND patient is known to have bone metastases, the liver specific alkaline phosphatase must be separated from the total and used to assess the liver function instead of the total alkaline phosphatase.
13)Patients willing and able to comply with the study protocol for the duration of the study.
14)Written informed consent prior to any study-specific screening procedures with the understanding that the patient may withdraw consent at any time without prejudice.
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 28
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 28
1)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.
2)Addiction to alcohol or drugs.
3)Need for metronidazole, warfarin and/or theophylline medication, the metabolism of which is likely influenced by disulfiram and copper, see Table 4.
4)Patients who are taking medications metabolized by cytochrome P450 2E1, including chlorzoxazone or halothane and its derivatives, see Table 4..
5)Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen.
6)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 (eg., 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.
7)Patients with meningeal carcinomatosis.
8)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.
9)Severe/uncontrolled intercurrent illness/infection.
10)Patients with organ allografts requiring immunosuppression.
11)Patients with known positive HIV status.
12)Hemochromatosis.
13)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.
14)Patients with pre-existing neuropathy > Grade 2.
15)Patients with other significant disease or disorders that, in the Investigator's opinion, would exclude the patient from the study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine the efficacy (as measured by objective response rate.) of vinorelbine, cisplatin and disulfiram and copper in patients with refractory metastatic hormone receptor positive, HER2 negative, breast cancer CTC_EMT positive.;Secondary Objective: To describe the progression-free survival, overall survival and toxic effects of vinorelbine, cisplatin , disulfiram and copper in patients with refractory metastatic breast cancer CTC_EMT positive.;Primary end point(s): Objective response rates;Timepoint(s) of evaluation of this end point: To be done every 3 cycles ±7 days until progression or start of new anticancer treatment. If study treatment is discontinued due to other reasons than progression, disease assessment must be done until progression every 9 weeks ± days.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Progression-free survival<br>Overall survival<br>Toxicity<br>Frequency of grade III and IV adverse events<br>Association between clinical outcome and biomarkers<br>;Timepoint(s) of evaluation of this end point: Progression free survival-untill progression or start of new anticancer therapy<br>Overall survival-untill end of trial or death or lost to follow up<br>Toxicity and adverse events-untill safety follow up<br>Association between clinical outcome and biomarkers-untill day 1 cycle 3