E7389 Versus Treatment of Physician's Choice in Patients With Locally Recurrent or Metastatic Breast Cancer

Inclusion Criteria

• Female patients with histologically or cytologically confirmed carcinoma of the breast.

Every effort should be made to make paraffin embedded tissue or slides from the diagnostic biopsy or surgical specimen available for confirmation of diagnosis.

• Patients with locally recurrent or metastatic disease who have received at least two (and not more than five) prior chemotherapeutic regimens for breast cancer, at least two of which were administered for treatment of locally recurrent and/or metastatic disease.

Prior therapy must be documented by the following criteria prior to entry onto study:

• Regimens must have included an anthracycline (e.g., doxorubicin, epirubicin) and a taxane (e.g., paclitaxel, docetaxel) in any combination or order. Treatment with any of these agents is not required if they are contraindicated for a certain patient.
• One or two of these regimens may have been administered as adjuvant and/or neoadjuvant therapy, but at least 2 must have been given for relapsed or metastatic disease.
• Patients must have proved refractory to the most recent chemotherapy, documented by progression on or within six (6) months of therapy.
• Patients with Human Epidermal Growth Factor 2 (HER2/neu) positive tumors may additionally have been treated with trastuzumab.
• Patients may have additionally been treated with anti-hormonal therapy.
• Resolution of all chemotherapy or radiation-related toxicities to Grade 1 severity or lower, except for stable sensory neuropathy = 18 years.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2.
• Life expectancy of >= 3 months.
• Adequate renal function as evidenced by serum creatinine = 40 mL/min per the Cockcroft and Gault formula.
• Adequate bone marrow function as evidenced by absolute neutrophil count (ANC) >= 1.5 x 10^9/L, hemoglobin >= 10.0 g/dL (a hemoglobin = 100 x 10^9/L.
• Adequate liver function as evidenced by bilirubin 3 x ULN (in absence of liver metastases) or > 5 x ULN (in presence of liver metastases) AND patient is known to have bone metastases, the liver specific alkaline phosphatase must be separated from the total and used to assess the liver function instead of the total alkaline phosphatase.
• Patients willing and able to comply with the study protocol for the duration of the study.
• 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 who have received any of the following treatments within the specified period before E7389 or TPC treatment start:
• chemotherapy, radiation, trastuzumab or hormonal therapy within three weeks.
• any investigational drug within four weeks.
• Radiation therapy encompassing > 30% of marrow.
• Prior treatment with mitomycin C or nitrosourea.
• Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen.
• 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 in this study. Any signs (e.g., radiologic) and/or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment; radiographic stability should be determined by comparing a contrast-enhanced computed tomography or magnetic resonance imaging brain scan performed during screening to a prior scan performed at least 4 weeks earlier.
• Patients with meningeal carcinomatosis.
• 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 if randomized to E7389 are not eligible. If a patient is to continue on mini-dose warfarin, then the prothrombin time (PT) or international normalized ratio (INR) must be closely monit