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

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.