A Study Comparing Eribulin Mesylate and Ixabepilone in Causing or Exacerbating Neuropathy in Patients With Advanced Breast Cancer

• Neuropathy assessed by patient neurotoxicity questionnaire and vibration sensibility. [ Time Frame: Assessments are performed at the start of Cycles 2-6 and every third cycle, end-of-treatment visit, and post-treatment follow-up. ] [ Designated as safety issue: Yes ]
• Incidence of myalgia/arthralgia AEs. [ Time Frame: From the time subject is consented to when she completes the either 21 day or 42 day post-treatment follow-up visit. ] [ Designated as safety issue: Yes ]
• General safety assessed by monitoring all AEs and serious AEs, laboratory measurements, vital signs, and physical exams. [ Time Frame: Safety is assessed from the time subject is consented to when she completes the either 21 day or 42 day post-treatment follow-up visit. ] [ Designated as safety issue: Yes ]
• Objective response rate, clinical benefit rate and progression-free survival based on investigator assessments according to Response Evaluation Criteria in Solid Tumors (RECIST). [ Time Frame: At Baseline, at the end of Cycles 2, 4 and 6, subsequently at the end of every third cycle, at the end-of-treatment, and at the post-treatment follow-up. ] [ Designated as safety issue: No ]

• Neuropathy assessed by patient neurotoxicity questionnaire and vibration sensibility. [ Time Frame: Assessments are performed at the start of Cycles 2-6 and every third cycle, end-of-treatment visit, and posttreatment follow-up. ] [ Designated as safety issue: Yes ]
• Incidence of myalgia/arthralgia AEs. [ Time Frame: From the time subject is consented to when she completes the either 21 day or 42 day posttreatment follow up visit. ] [ Designated as safety issue: Yes ]
• General Safety assessed by monitoring all AEs and serious AEs, laboratory measurements, vital signs, and physical exams. [ Time Frame: Safety is assessed from the time subject is consented to when she completes the either 21 day or 42 day post treatment follow up visit. ] [ Designated as safety issue: Yes ]
• Response rate, clinical benefit rate and progression-free survival based on investigator assessments according to Response Evaluation Criteria in Solid Tumors (RECIST). [ Time Frame: At Baseline, at the end of Cycles 2, 4 and 6, subsequently at the end of every third cycle, at the end-of-treatment, and at the posttreatment follow-up. ] [ Designated as safety issue: No ]

The purpose of this study in patients with advanced breast cancer is to compare the incidence and severity of neuropathy adverse events for the two treatment groups (eribulin versus ixabepilone) using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 3.0) grading.

• Drug: eribulin mesylate

  E7389 (eribulin mesylate) given at a dose of 1.4 mg/m^2 as a 2 - 5 minute intravenous (IV) bolus on Days 1 and 8 of a 21-day cycle.

  The Treatment Phase will include six cycles. Patients may enter the Extension Phase for additional cycles following the sixth cycle of treatment.

  Other Name: E7389
• Drug: ixabepilone

  Ixabepilone given at a starting dose of 32 or 40 mg/m^2 (as per approved labeling) as a 3-hour IV infusion on Day 1 of a 21-day cycle.

  The Treatment Phase will include six cycles. Patients may enter the Extension Phase for additional cycles following the sixth cycle of treatment.

• Active Comparator: 1
  Intervention: Drug: eribulin mesylate
• Active Comparator: 2
  Intervention: Drug: ixabepilone

Inclusion criteria:

1. Female subjects with confirmed locally recurrent or metastatic carcinoma of the breast who have received prior taxane therapy and at least one prior cytotoxic chemotherapy regimen for advanced disease.

Exclusion criteria:

1. Subjects who have received prior ixabepilone therapy.
2. Subjects with prior participation in an eribulin clinical study, even if not assigned to eribulin treatment.
3. Subjects with pre-existing neuropathy Grade greater than or equal to 2.
4. Subjects with a history of diabetes mellitus Type 1 or 2.
5. Subjects with bilateral mastectomy which included bilateral axillary lymph node dissection.
6. Subjects with missing digits required for vibration assessment.
7. Subjects with any other concurrent diseases or conditions that would be expected to interfere with neuropathy assessments, which may include vitamin deficiency, sequelae of cerebrovascular disease, thyroid insufficiency, lumbar or cervical radiculopathy, or alcoholic or inflammatory neuropathy.