Study to Evaluate the Efficacy, Safety, and Tolerability of E7070 in Metastatic Breast Cancer Patients

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.