A Phase II Trial Of Trastuzumab Plus Weekly Ixabepilone (BMS-247550) And Carboplatin In Patients With HER/Neu-Positive Metastatic Breast Cancer

Inclusion Criteria

Inclusion criteria:

- Histologically confirmed adenocarcinoma of the breast

- Metastatic disease

- HER2/neu-positive (3+) disease by immunohistochemistry or fluorescent in situ
hybridization

- At least 1 objectively measurable disease parameter

- No brain metastases as the only site of measurable disease

- Previously irradiated tumors are not considered measurable disease, except for
recurrent disease located in an area of prior adjuvant irradiation (e.g., axilla
or chest wall)

- Age >= 18

- ECOG performance status of 0-1

- Granulocyte count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- AST and ALT ≤ 1.5 times upper limit of normal (ULN) (2.0 times ULN for patients with
liver involvement by tumor)

- Creatinine ≤ 1.5 mg/dL

- LVEF within lower limit of normal by MUGA or echocardiogram

- Negative pregnancy test

- Fertile patients must use effective nonhormonal contraception

- At least 1 week since prior hormonal therapy

- At least 2 weeks since prior radiotherapy

Exclusion criteria:

- Untreated brain metastases

- Previously treated brain metastases that have responded to prior radiotherapy
and/or surgery are allowed

- New York Heart Association class III or IV heart disease

- Pregnant or nursing

- Prior severe (grade 3 or 4) hypersensitivity reaction to drugs formulated in
polyoxyethylated castor oil (Cremophor EL)

- Peripheral neuropathy

- Other malignancy within the past 5 years except curatively treated basal cell or
squamous cell skin cancer or carcinoma in situ of the cervix

- Prior trastuzumab (Herceptin®) for metastatic disease

- Concurrent pegfilgrastim

- Prior ixabepilone for metastatic disease

- Prior carboplatin or other chemotherapy for metastatic disease

- Prior cumulative doxorubicin dose > 360 mg/m^2

- Prior cumulative epirubicin dose > 640 mg/m^2

- Concurrent hormonal therapy

- Concurrent radiotherapy, including radiotherapy for brain metastases