| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| breast cancer |
| karcinóm prsníka |
|
| E.1.1.1 | Medical condition in easily understood language |
| breast cancer |
| karcinóm prsníka |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10006187 |
| E.1.2 | Term | Breast cancer |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| 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. |
|
| E.2.2 | Secondary objectives of the trial |
| 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. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
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.
|
|
| E.4 | Principal exclusion criteria |
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.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
|
| E.5.1.1 | 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. |
|
| E.5.2 | Secondary end point(s) |
Progression-free survival
Overall survival
Toxicity
Frequency of grade III and IV adverse events
Association between clinical outcome and biomarkers
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Progression free survival-untill progression or start of new anticancer therapy
Overall survival-untill end of trial or death or lost to follow up
Toxicity and adverse events-untill safety follow up
Association between clinical outcome and biomarkers-untill day 1 cycle 3 |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
This study was designed as a single-stage, phase II which required a total of 28 patients to discriminate between true CBRs of ≤5% and ≥20% at a type I error of 5% and a type II error of 16%. If 4 or more patients had a CR, PR, or SD > 6 months, treatment would be considered to have activity in this patient population and would merit further clinical study.
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
