An Open Label Phase I Study of Humanized Human Milk Fat Globule-1 (huHMFG1) Antibody in Patients With Locally Advanced or Metastatic Breast Cancer (TOPCAT)

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed breast cancer

- Locally advanced or metastatic disease

- No inflammatory breast cancer

- Measurable (RECIST) or evaluable disease (e.g., cytologically or radiologically
detectable disease that does not fulfill RECIST criteria)

- Failed prior OR not a candidate for OR refused anthracycline- and taxane-containing
chemotherapy

- Patients whose tumor overexpresses HER-2 must have failed prior trastuzumab
(Herceptin®)

- No known CNS metastases

- No metastases accessible to complete surgical resection

- Unstained slides cut from formalin-fixed and paraffin-embedded tumor blocks available

- Appropriate tumor block also acceptable

- Hormone receptor status:

- Not specified

PATIENT CHARACTERISTICS:

Age

- 18 and over

Sex

- Female

Menopausal status

- Not specified

Performance status

- WHO 0-1

Life expectancy

- At least 4 months

Hematopoietic

- Hemoglobin ≥ 10 g/dL

- Absolute neutrophil count ≥ 1,500/mm^3

- WBC ≥ 1,000/mm^3

- Platelet count ≥ 100,000/mm^3

Hepatic

- Bilirubin ≤ 1.5 mg/dL

- ALT or AST ≤ 2.5 times upper limit of normal (ULN) (< 5 times ULN in patients with
liver metastases) OR

- Alkaline phosphatase ≤ 2.5 times ULN (< 5 times ULN in patients with liver
metastases)

- Any degree of elevated alkaline phosphatase allowed provided it is due to bone
metastases

Renal

- Creatinine ≤ 1.5 times ULN OR

- Creatinine clearance > 60 mL/min

- Uric acid < 1.25 times ULN (for patients with hyperuricemia only)

- Calcium (corrected for serum albumin) < 11.5 mg/dL (for patients with hypercalcemia
only)

Cardiovascular

- LVEF ≥ 45% by MUGA or echocardiogram within the past 4 weeks

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective barrier contraception

- No other malignancy within the past 5 years except adequately treated nonmelanoma
skin cancer or cervical intra-epithelial neoplasia

- No other uncontrolled illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

- See Disease Characteristics

- Prior biological therapy allowed

- More than 2 weeks since prior blood transfusions or growth factors to aid
hematological recovery

- No other concurrent antitumor immunotherapy

Chemotherapy

- See Disease Characteristics

- More than 4 weeks since prior cytotoxic chemotherapy

- No more than 3 prior chemotherapy regimens, including adjuvant/neoadjuvant therapy

- No concurrent antitumor chemotherapy

Endocrine therapy

- Prior hormonal therapy allowed

- No concurrent corticosteroids except as physiologic replacement and/or for acute
short-term treatment of, or prophylaxis against, infusion reactions

- No concurrent antitumor hormonal therapy

Radiotherapy

- See Disease Characteristics

- More than 4 weeks since prior radiotherapy (except for palliative radiotherapy)

- No concurrent antitumor radiotherapy, except for palliation to non-study lesions

- Irradiated area should be as small as possible and involve ≤ 10% of the bone
marrow in any given 4-week period

Surgery

- More than 4 weeks since prior major surgery

Other

- More than 30 days since prior investigational agents

- No other concurrent investigational agents