• Time to disease progression [ Designated as safety issue: No ]
• Time to treatment failure [ Designated as safety issue: No ]
• Overall survival [ Designated as safety issue: No ]
• Toxicity [ Designated as safety issue: Yes ]

• Time to disease progression
• Time to treatment failure
• Overall survival
• Toxicity

RATIONALE: Monoclonal antibodies, such as trastuzumab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as ixabepilone and carboplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining trastuzumab with ixabepilone and carboplatin may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving trastuzumab together with ixabepilone and carboplatin works in treating patients with HER2/neu-positive metastatic breast cancer.

OBJECTIVES:

Primary

• Determine the response rate in patients with HER2/neu-positive metastatic breast cancer treated with trastuzumab (Herceptin®), ixabepilone, and carboplatin.

Secondary

• Determine the time to disease progression and time to treatment failure in patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.
• Determine the overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

• Induction therapy: Patients receive trastuzumab (Herceptin®) IV over 30 minutes* on days 1, 8, 15, and 22 and ixabepilone IV over 1 hour and carboplatin IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of unacceptable toxicity.

NOTE: *Trastuzumab is given over 90 minutes on day 1 of course 1 (induction therapy) only.

• Maintenance therapy: Patients receive trastuzumab IV over 90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years from study entry.

PROJECTED ACCRUAL: A total of 10-60 patients will be accrued for this study within 1-6 months.

• Biological: trastuzumab
• Drug: carboplatin
• Drug: ixabepilone

DISEASE CHARACTERISTICS:

• 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)

• No untreated brain metastases

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

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Male or female

Menopausal status

• Not specified

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

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

Renal

• Creatinine ≤ 1.5 mg/dL

Cardiovascular

• LVEF within lower limit of normal by MUGA or echocardiogram
• No New York Heart Association class III or IV heart disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective nonhormonal contraception
• No prior severe (grade 3 or 4) hypersensitivity reaction to drugs formulated in polyoxyethylated castor oil (Cremophor EL)
• No peripheral neuropathy
• No 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 CONCURRENT THERAPY:

Biologic therapy

• No prior trastuzumab (Herceptin®) for metastatic disease
• No concurrent pegfilgrastim

Chemotherapy

• No prior ixabepilone for metastatic disease
• No prior carboplatin for metastatic disease
• No other prior chemotherapy for metastatic disease
• No prior cumulative doxorubicin dose > 360 mg/m^2
• No prior cumulative epirubicin dose > 640 mg/m^2

Endocrine therapy

• Prior hormonal therapy for metastatic disease allowed
• At least 1 week since prior hormonal therapy
• No concurrent hormonal therapy

Radiotherapy

• See Disease Characteristics
• At least 2 weeks since prior radiotherapy
• No concurrent radiotherapy, including radiotherapy for brain metastases

Surgery

• See Disease Characteristics

• National Cancer Institute (NCI)
• North Central Cancer Treatment Group