• Objective response rate (partial and complete response) [ Designated as safety issue: No ]
  

• 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 ]
  

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.

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