RATIONALE: Drugs used in chemotherapy, such as ABI-007 and carboplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining ABI-007 and carboplatin with trastuzumab may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining ABI-007 and carboplatin with trastuzumab in treating patients who have HER2/neu-overexpressing metastatic breast cancer.

Condition	Treatment or Intervention	Phase
stage IV breast cancer recurrent breast cancer	Drug: ABI-007  Drug: carboplatin  Drug: trastuzumab  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: monoclonal antibody therapy	Phase II

OBJECTIVES: Primary

• Determine the safety and tolerability of trastuzumab (Herceptin®), ABI-007, and carboplatin in patients with HER2/neu-overexpressing metastatic breast cancer.
• Determine the objective response rate in patients treated with this regimen.

Secondary

• Determine the duration of response in patients treated with this regimen .
• Determine the time to disease progression in patients treated with this regimen.
• Determine the survival of patients treated with this regimen.

OUTLINE: This is an open-label study.

Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on days 1, 8, 15, and 22. Patients also receive ABI-007 IV over 30 minutes followed immediately by carboplatin IV over 30-60 minutes on days 1, 8, and 15. Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity.

The first group of 3 patients receives a lower dose of ABI-007 for the first course. If no more than 1 of 3 patients experiences unacceptable toxicity, the dose of ABI-007 is escalated once for all subsequent courses and patients.

After 6 courses of therapy, patients continue to receive trastuzumab once weekly in the absence of disease progression or unacceptable toxicity. Patients may continue to receive ABI-007 and carboplatin beyond 6 courses at the discretion of the investigator.

Patients are followed monthly for 3 months and then every 3 months for 2 years.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study within 18 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the breast
• Stage IV disease
• Measurable disease
• At least 2.0 cm except for pulmonary lesions that are well documented as ≥ 1.0 cm by CT scan
• Disease located completely outside the radiotherapy portal OR there is histological confirmation of progressive disease within the radiotherapy portal
• Overexpression of HER2/neu, as demonstrated by one of the following:
• 3+ overexpression by immunohistochemistry (IHC) OR fluorescence hybridization (FISH)-positive for HER2/neu gene amplification
• 2+ overexpression by IHC AND FISH-positive
• No parenchymal brain metastases unless documented to be clinically and radiographically stable for at least 6 months after prior therapy
• Hormone receptor status:
• Not specified

PATIENT CHARACTERISTICS: Age

• Over 18

Sex

• Not specified

Menopausal status

• Not specified

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9 g/dL

Hepatic

• AST and ALT ≤ 2.5 times upper limit of normal (ULN)
• Bilirubin normal
• Alkaline phosphatase ≤ 2.5 times ULN (unless bone metastases are present AND liver metastases are absent)

Renal

• Creatinine ≤ 1.5 mg/dL

Cardiovascular

• LVEF normal by MUGA or echocardiogram
• No congestive heart failure

Other

• No other serious medical or psychiatric illness
• No serious active infection
• No other malignancy within the past 5 years that would preclude diagnosis or assessment of breast cancer
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy

• More than 1 year since prior adjuvant trastuzumab (Herceptin®)
• No other concurrent immunotherapy

Chemotherapy

• No more than 1 prior chemotherapy regimen for metastatic disease
• Prior neoadjuvant or adjuvant chemotherapy allowed
• At least 1 year since prior taxane
• At least 3 weeks since prior cytotoxic chemotherapy and recovered
• Prior cumulative lifetime dose of doxorubicin ≤ 360 mg/m^2 as neoadjuvant or adjuvant therapy or first-line therapy for metastatic disease
• No other concurrent chemotherapy

Endocrine therapy

• No concurrent antitumor hormonal therapy

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy and recovered
• No concurrent radiotherapy

Surgery

• At least 4 weeks since prior major surgery and recovered

Other

• More than 3 weeks since prior investigational drugs
• Concurrent bisphosphonates allowed
• No concurrent participation in another study involving investigational procedures or drugs

New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting

Study chairs or principal investigators

Andrew D. Seidman, MD,  Principal Investigator,  Memorial Sloan-Kettering Cancer Center   
Clifford A. Hudis, MD,  Principal Investigator,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000370829; MSKCC-04018; ABI-CA016
Record last reviewed:  May 2004
Record first received:  June 10, 2004
ClinicalTrials.gov Identifier:  NCT00085605
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-10-22