Study of E7389 for Advanced or Metastatic Breast Cancer

The purpose of this study (E7389-J081-224; hereafter referred to as Study 224) is to evaluate the safety of patients who continue to receive E7389 after completing the Phase II clinical study (E7389-J081-221; hereafter referred to as Study 221) of E7389 for advanced or relapsed breast cancer by intravenously administering E7389.

Study 224 (Extension Period) was designed to evaluate the safety and efficacy of E7389 by collecting data from subjects who continued receiving E7389 after being transferred from Study 221 (Core Period). Thus, efficacy analyses performed in Study 221 were updated and reported with the additional data collected in Study 224. Objective response rate (ORR) and the number of subjects with adverse events are reported as outcome measures because these were the outcome measures of Study 221 which is a main study in the combined data. Also, safety analyses performed in Study 221 were updated and reported with the additional data collected in Study 224.

Eligibility Criteria:
Inclusion criteria:

1. Female patients with histologically or cytologically confirmed breast cancer.
2. Patients who have received prior chemotherapy including anthracycline and taxane.
3. Patients aged 20 - 74 years when giving informed consent and who have given written voluntary consent for participating in this study before the completion of Study 221.
4. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2.
5. Patients with a measurable lesion.
6. Patients with an expected survival of ≥ 3 months from the start of study drug therapy.
7. Female patients in whom continued administration of E7389 following Study 221 will be useful.
8. Patients who have met the criteria for starting the next cycle in Study 221.

Namely, patients who meet all of the following criteria:

1. Neutrophil count \>= 1,500 /µL
2. Platelet count \>= 100,000 /µL
3. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<= 2.5 times the upper limit of normal (ULN) in the facility or \<= 5 times ULN in patients with hepatic metastasis)
4. Total bilirubin \<= 1.5 times ULN
5. Serum creatinine \<= 1.5 times ULN
6. Non-hematological toxicity \<= Grade 2 (excluding disease-associated events and laboratory abnormalities without clinical symptoms)

Exclusion criteria:

1. Patients with systemic infection with a fever (≥38.0°C).
2. Patients with pleural effusion, ascites or pericardial fluid requiring drainage.
3. Patients with brain metastasis presenting clinical symptoms.
4. Pregnant women, nursing mothers, or premenopausal women of childbearing potential. Premenopausal women of childbearing potential are defined as women who are \<12 months after the latest menstruation and are positive in pregnancy test performed for enrollment or who have not taken the test and do not consent to take an appropriate contraceptive measure. Post-menopausal women must be amenorrheic for at least 12 months to make sure that they have no potential for becoming pregnant.
5. Patients with serious complications:

   1. Patients with uncontrollable cardiac disease such as ischemic heart disease and arrhythmia at a level of severity that needs to be treated (excluding left ventricular hypertrophy, mild left ventricular volume overload and mild right leg block that accompany hypertension)
   2. Patients with myocardial infarction within 6 months prior to study entry
   3. Patients with a complication of hepatic cirrhosis
   4. Patients with interstitial pneumonia and pulmonary fibrosis
   5. Patients with a bleeding tendency
6. Patients with an active double cancer.
7. Pregnant women or nursing mothers.
8. Patients who have received extensive radiotherapy (≥30% of bone marrow).
9. Patients who refuse to receive the supportive therapy of blood transfusion for myelosuppression.
10. Patients who are participating in other clinical studies.
11. Patients who are judged by the principal investigator or the other investigators to be inappropriate as patients in this clinical study.