An Open-Label Phase II Study of E7070 in Metastatic Breast Cancer Patients Previously Treated With an Anthracycline, a Taxane, and Capecitabine

Fecha de inicio: 1 de febrero de 2004

Inclusion Criteria: * Patients must be female, * Patients must have histologically or cytologically confirmed metastatic breast cancer, * Patients must either have tumors that are resistant/refractory to chemotherapy with an anthracycline, a taxane, capecitabine, and appropriate Herceptin therapy, or tumors that cannot be treated with these agents due to patient's treatment toxicity; therefore, patients must have received 2 prior chemotherapies but no more than 3 prior chemotherapies in the metastatic setting, * Patients must have at least one uni-dimensionally measurable lesion according to the RECIST criteria in at least one site that has not been irradiated, * Patients must be aged \>= 18 years, * Patients must have a Karnofsky Performance Status of \>= 70%, * Patients must have a life expectancy of \>= 3 months, * Patients must have adequate renal function as evidenced by serum creatinine \<= 1.5 mg/dL, or if \> 1.5 but \<= 1.8 mg/dL, then a creatinine clearance of \>= 45 mL/min, * Patients must have adequate bone marrow function as evidenced by absolute neutrophil count of \>= 1.5 x 109/L, hemoglobin \>= 9.0 g/dL, and platelet count \>= 100 x 109/L, * Patients must have adequate liver function as evidenced by bilirubin of \<= 1.5 times the upper limits of normal (ULN); alkaline phosphatase \<= 3 times ULN and alanine transaminase (ALT) and aspartate transaminase (AST) \<= 3 times ULN, unless related to liver metastasis, in which case \<= 5 x ULN, * Patients must have serum electrolytes including calcium (corrected for albumin), magnesium, and potassium (corrected) within normal limits, * Patients must be willing and able to complete the FACT-B questionnaire, * Patients must be willing and able to comply with the study protocol for the duration of the study, and * Patients must give written informed consent prior to any study specific screening procedures with the understanding that the patient may withdraw consent at any time without prejudice. Exclusion Criteria: * Patients must not have metastatic disease that can be completely surgically resected, * Patients who received adjuvant taxane must not have experienced disease progression within 12 months of beginning that therapy, * Patients must not have received chemotherapy, hormonal therapy, or Herceptin within 2 weeks of E7070 treatment start and must have recovered from any chemotherapy-related or other therapy-related toxicity at study entry, * Patients must not have received investigational drugs including immunotherapy, gene therapy, or other biologic therapy; antineoplastic therapy; or radiation therapy (other than required for palliation of bone pain or chest ulceration) within 2 weeks of E7070 treatment, * Patients must not have received prior treatment with Mitomycin C or nitrosoureas, * Patients must not have undergone high dose chemotherapy with hematopoietic stem cell rescue, * Patients must not have untreated brain metastases (Patients who have been treated for central nervous system (CNS) metastases must be asymptomatic and radiologically stable \[not receiving radiation\] and must not have been receiving steroids for 4 weeks prior to entry. Patients without known CNS metastases who are symptomatic for CNS metastasis must be evaluated with a CT scan or MRI scan prior to E7070 treatment.), * Patients must not have had major surgery without full recovery within 4 weeks of E7070 treatment start, * Patients must not have pulmonary lymphatic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen, * Patients must not have leptomeningeal metastasis, * Patients must not have evidence of clinically relevant ascites or pleural effusion requiring more than one isolated paracentesis or pleurocentesis per month prior to study start, * Patients must not be expected to require more than one isolated paracentesis or pleurocentesis per month during the study for the treatment of clinically relevant ascites or pleural effusion, * Patients must not be pregnant or breast-feeding and must practice adequate contraception if not surgically sterile, * Patients must not have severe medically uncontrolled intercurrent illness/infection, * Patients must not have had unstable angina or myocardial infarction in the past 6 months, * Patients must not have serious cardiac arrhythmia or symptomatic congestive heart failure \>= Grade II (NYHA classification), * Patients must not have a history of prolonged QT, QTc \> 470 ms (Bazett's correction) at entry, or history of torsade de pointes, * Patients must not have recent history (\<= 12 months) of active or chronic viral hepatitis, * Patients must not have organ allografts, * Patients must not have known history of HIV positivity, * Patients must not have a history of hypersensitivity to sulfonamides, * Patients must not have a history of uncontrolled seizures, * Patients must not have had a prior malignancy, other than carcinoma in situ of the cervix or nonmelanoma skin cancer, unless the prior malignancy was diagnosed and definitively treated \>= 5 years previously with no subsequent evidence of recurrence, or * Patients must not have other significant disease or disorders that, in the Investigator's opinion, would exclude the patient from the study.