Locally advanced or metastatic breast cancer MedDRA version: 8.1 Level: PT Classification code 10055113
Conditions
Interventions
Product Name: BOLD
Product Code: E7389
Pharmaceutical Form: Solution for injection
CAS Number: 441045-17-6
Current Sponsor code: E7389
Other descriptive name: BOLD
Concentration unit: µg/ml microgram(
Sponsors
Eisai Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Female patients with histologically or cytologically confirmed carcinoma of the breast. Every effort should be made to ensure that paraffin embedded tissue or slides from the diagnostic biopsy or surgical specimen are available for confirmation of diagnosis. 2. Patients with locally advanced or metastatic disease who have received either one anthracycline-taxane combination chemotherapy, or two prior therapies, including an anthracycline-based regimen without a taxane, and a taxane-based regimen. The order in which the regimens were received is unimportant. The treatments may have been administered as adjuvant or neoadjuvant chemotherapy and/or for the treatment of advanced or metastatic disease. • Regimens must have included an anthracycline (e.g. doxorubicin, epirubicin) and a taxane (e.g. paclitaxel, docetaxel), either in combination or in separate regimens. •Patients must have progressed during or after their last anti-cancer therapy, and this must be documented. • Patients with known HER2/neu over-expressing tumors must additionally have been treated with trastuzumab in centers where this treatment is available • Patients with known estrogen and/or progesterone receptor-expressing tumors may have additionally been treated with hormonal therapy 3. Resolution of all chemotherapy or radiation-related toxicities to Grade 1 severity or lower, except for stable sensory neuropathy =Grade 2 and alopecia 4. Age = 18 years 5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2. 6. Life expectancy of = 3 months 7. Adequate renal function as evidenced by serum creatinine = 2.0 mg/dL or calculated creatinine clearance = 40 mL/minute (min) per the Cockcroft and Gault formula 8. Adequate bone marrow function as evidenced by absolute neutrophil count (ANC) = 1.5 x 10*/L, hemoglobin = 10.0 g/dL (a hemoglobin =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patients who have received more than two prior chemotherapy regimens for their disease, including adjuvant therapies (other therapies are allowed e.g. anti-estrogens, trastuzumb and radiotherapy) 2. Patients who have received capecitabine as a prior therapy for their disease 3. Patients who have received chemotherapy, radiation, hormonal therapy, or trastuzumab within three weeks of E7389 treatment start 4. Radiation therapy encompassing > 30% of marrow 5. Prior high dose chemotherapy with hematopoietic stem cell rescue 6. Prior treatment with mitomycin C or nitrosourea 7. Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen 8. 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 with E7389. Any signs (e.g. radiologic) and/or symptoms of brain metastases must be stable for at least 4 weeks. 9. Patients with meningeal carcinomatosis 10. Patients who are receiving anti-coagulant therapy with warfarin or related compounds, other than for line patency, and cannot be changed to heparin-based therapy, are not eligible. If a patient is to continue on mini-dose warfarin, then the prothrombin time (PT) / international normalized ratio (INR) must be closely monitored. 11. 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 (considered to be two methods of contraception, one of which must be a barrier method, e.g., condom, diaphragm or cervical cap). Perimenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. 12. Severe/uncontrolled intercurrent illness/infection 13. Significant cardiovascular impairment (history of congestive heart failure > NYHA grade II, unstable angina or myocardial infarction within the past six months, or serious cardiac arrhythmia) 14. Patients with organ allografts requiring immunosuppression 15. Patients with known positive HIV status 16. Patients who have had a prior malignancy, other than 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 17. Patients with pre-existing neuropathy > Grade 2 18. Patients with a hypersensitivity to halichondrin B and/or halichondrin B chemical derivative 19. Patients who participated in a prior E7389 clinical trial 20. Patients with other significant disease or disorders that, in the Investigator’s opinion, would exclude the patient from the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of E7389 versus capecitabine monotherapy, in terms of Overall Survival and Progression-Free Survival in patients with locally advanced or metastatic breast cancer;Secondary Objective: To assess and compare between the two treatment groups: • Quality of Life measured using the EORTC questionnaire • Objective Tumor Response Rate as measured using RECIST criteria • Duration of Response • One, Two and Three year Survival • Tumor Related Symptom Assessments measured by pain intensity (VAS), and analgesic consumption • Safety Parameters (adverse events, laboratory parameters, concomitant medication, and study drug exposure) To investigate pharmacokinetic/pharmacodynamic relationships in a population pharmacokinetic study in a minimum of 200 patients in the E7389 arm ;Primary end point(s): Overall Survival is measured from the date of randomization until date of death from any cause or the last date the patient was known to be alive. Progression-Free Survival is measured from the date of randomization to the date of recorded progression of the disease or the death of the patient from any cause. | — |
Countries
Belgium, Bulgaria, Czech Republic, France, Germany, Greece, Hungary, Italy, Lithuania, Spain
Outcome results
None listed