OBJECTIVES:

• Determine the safety and tolerability of monoclonal antibody HuHMFG1 in women with locally advanced or metastatic breast cancer previously treated with anthracycline and taxane-based therapy.
• Determine the maximum tolerated dose and appropriate schedule of this drug in these patients.
• Determine the pharmacokinetic profile of this drug in these patients.
• Determine the tumor response rate, progression-free survival, and median survival of patients treated with this drug.
• Analyze immunological markers for evaluation of disease status (e.g., in vitro analysis of antibody-dependent cellular cytotoxicity, natural killer cell activity, complement depletion, and tumor markers CA 15.3 and CEA) in patients treated with this drug.

OUTLINE: This is a dose-escalation, open-label, nonrandomized, multicenter study.

• Phase I: Patients receive monoclonal antibody HuHMFG1 IV over 1-3 hours once every 3 weeks for doses 1 and 2. All subsequent dose intervals are based on individual half-life value of the drug. Patients receive at least 6 doses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of monoclonal antibody HuHMFG1 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

• Phase II:Patients receive monoclonal antibody HuHMFG1 as above at the MTD. Patients are followed at 28 days.

PROJECTED ACCRUAL: Approximately 3-40 patients (3-15 patients for phase I and 19-25 patients for phase II) will be accrued for this study within approximately 12 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed breast cancer

  • Locally advanced or metastatic disease
  • No inflammatory breast cancer
• Polymorphic epithelial mucin (PEM) antigen overexpression by immunohistochemistry

• Previously treated with an anthracycline and a taxane in any combination for breast cancer

  • No more than 2 prior chemotherapy regimens, including adjuvant /neoadjuvant therapy
  • No more than 1 prior regimen for distant metastatic disease
  • Any number of prior hormonal or biologic therapy regimens allowed

• Measurable disease

  • At least one unidimensionally measurable lesion not previously irradiated

  • The following are not considered measurable lesions:

    • Bone
    • Leptomeningeal disease
    • Ascites
    • Pleural/pericardial effusion
    • Lymphangitis cutis/pulmonis
    • Abdominal masses not confirmed and followed by imaging techniques
    • Cystic lesions
• No metastases accessible to complete surgical resection
• No CNS metastasis by CT scan

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Female

Menopausal status

• Not specified

Performance status

• WHO 0-2

Life expectancy

• At least 4 months

Hematopoietic

• Hemoglobin at least 10 g/dL
• Neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 1.5 mg/dL
• ALT and AST no greater than 2.5 times upper limit of normal (ULN) (less than 5 times ULN if liver metastases are present)

Renal

• Creatinine no greater than 1.5 times ULN OR
• Creatinine clearance greater than 60 mL/min
• No hyperuricemia (uric acid at least 1.25 times ULN)
• No hypercalcemia (calcium at least 11.5 mg/dL [corrected for serum albumin])

Cardiovascular

• LVEF at least 45% by MUGA or echocardiogram within the past 4 weeks

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3-6 months after study participation
• No other prior malignancy within the past 5 years except adequately treated nonmelanoma skin cancer or cervical intraepithelial neoplasia
• No other concurrent uncontrolled comorbid illness that represents unacceptable risk in the opinion of the investigator
• No legal incapacity

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• More than 2 weeks since prior growth factors to aid hematologic recovery
• No other concurrent immunotherapy

Chemotherapy

• See Disease Characteristics
• More than 4 weeks since prior cytotoxic chemotherapy
• No concurrent chemotherapy for metastatic breast cancer

Endocrine therapy

• See Disease Characteristics
• No concurrent endocrine therapy for metastatic breast cancer
• No concurrent chronic corticosteroid therapy
• No concurrent high-dose corticosteroids

Radiotherapy

• More than 4 weeks since prior radiotherapy except for palliation
• No concurrent antitumor radiotherapy except for palliation

Surgery

• More than 4 weeks since prior major surgery

Other

• More than 2 weeks since prior blood transfusions to aid hematologic recovery
• No participation in any other investigational drug study
• No other concurrent investigational drugs
• No other concurrent antitumor therapy