Ixabepilone + Carboplatin Metastatic Breast Cancer

Inclusion Criteria

Male or female patients will be eligible for inclusion in this study if they meet all of the following criteria:

• Has measurable metastatic and or locally unresectable breast cancer with documented HER2 negative (-) disease
• Has at least 1 measurable lesion per RECIST criteria (lesions that can be accurately measured in at least 1 dimension (longest diameter (LD) to be recorded) as ≥20 mm with conventional techniques (CT, MRI, X-ray) or as ≥10 mm with spiral CT scan). Irradiated lesions cannot be used to assess response but can be used to assess progression.
• Has received up to 2 (0 to 2) prior chemotherapy regimens for metastatic disease with the following conditions:

•Has had no prior treatment with ixabepilone or platinum agents

• Has had no adjuvant chemotherapy within the 6 months prior to study, but may have received prior anthracyclines and/or taxanes as adjuvant chemotherapy
• 3 weeks or more have elapsed since last chemotherapy treatment and any related toxicities have resolved to 50 mL/min (based on Cockroft and Gault method [Appendix III]) Platelet count ≥100,000 x 106/L
• If patient has had radiation therapy, it has been completed >3 weeks prior to the start of study treatment. NOTE: Previously irradiated lesions will not be evaluable. However, these patients will still be eligible.
• Has a negative serum pregnancy test within 7 calendar days prior to registration (female patients of childbearing potential [not surgically sterilized and between menarche and 1 year postmenopause
• If fertile, patient (male or female) has agreed to use an acceptable method of birth control to avoid pregnancy for the duration of the study and for a period of 3 months thereafter
• Has signed the most recent Patient Informed Consent Form
• Has signed a Patient Authorization Form Note: Having tissue available is not an inclusion criterion in this study; however, available tissue will be collected (see Section 8) if possible.

Exclusion Criteria

A patient will be excluded from this study if he or she meets any of the following criteria:

• Had prior treatment with ixabepilone or other epothilones
• Had prior radiation to ≥30% of major bone marrow containing areas (pelvis, lumbar spine)
• Has ER+ and/or PR+ disease that has not progressed on hormone therapy, unless the patient has life-threatening or rapidly progressing visceral disease
• Has HER2+ disease (IHC staining of 3+ [uniform, intense membrane staining of >30% of invasive tumor cells]), a FISH result of more than 6 HER2 gene copies per nucleus or a FISH ratio (HER2 gene signals to chromosome 17 signals of >2.2)
• Has only lytic bone disease or nonmeasurable disease only
• Has a known, prior, severe (NCI CTCAE Grade 3-4) history of hypersensitivity reaction to a drug formulated in Cremophor®EL (polyoxyethylated castor oil) or has history of severe allergic reactions to cisplatin or other platinum-containing compounds
• Has been treated previously with a platinum-containing agent
• Is receiving concurrent immunotherapy, hormonal therapy, or radiation therapy. Washout periods for these prior therapies are specified in Section 5.
• Is receiving concurrent investigational therapy or has received such therapy within the 30 days prior to dosing Day 1
• Has neuropathy (motor or sensory) >Grade 1
• Has evidence of CNS involvement requiring radiation or steroid treatment. Patients with stable brain metastases who are off steroids at least 2 weeks are eligible.
• Has a serious uncontrolled intercurrent medical or psychiatric illness, including serious infection
• Has clinically relevant coagulopathy either secondary to hepatic dysfunction or an underlying condition requiring therapeutic anticoagulation (specifically, A-fib, history of DVT). A daily aspirin or Plavix for CAD are permitted.
• Has a history of other malignancy within the last 5 years (except cured basal cell carcinoma of skin and carcinoma in situ of uterine cervix),