Trastuzumab and Interleukin-2 in Treating Patients With Metastatic Breast Cancer

PRIMARY OBJECTIVES:

I. To estimate the response rate and toxicity to low-dose IL-2 with intermediate-"pulse" dose interleukin 2 (IL-2) and trastuzumab in patients with uni-dimensional measurable metastatic breast cancer and human epidermal growth factor receptor 2 (HER2) positive (3+ overexpression by immunohistochemistry [IHC] method or positive by fluorescent in situ hybridization [FISH]) who either have had evidence of progressive disease while receiving a trastuzumab-containing regimen, or have had progressive disease within 12 months of receiving a trastuzumab-containing regimen.

SECONDARY OBJECTIVES:

I. To perform correlative immunologic assays to determine the degree of natural killer (NK) cell expansion in response to low-dose IL-2, and the effectiveness of patients' peripheral blood mononuclear cells (PBMC) in a standard antibody-dependent cell-mediated cytotoxicity (ADCC) assay directed against a HER2 target cell.

II. To determine the pharmacokinetics of trastuzumab using an every 2-week schedule.

III. To determine Fc-gamma receptor polymorphisms from study patients.

OUTLINE: This is a multicenter study.

Patients receive trastuzumab intravenously (IV) over 30-90 minutes on days 1 and 8 and aldesleukin subcutaneously (SC) on days 2-7 and 9-21. Beginning on day 22, patients receive trastuzumab IV over 30 minutes every 14 days. Patients also receive aldesleukin SC daily on days 1-14. Treatment continues for 1 year in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for at least 30 days.

PROJECTED ACCRUAL: A total of 17-37 patients will be accrued for this study.

Inclusion criteria

• Histologically or cytologically confirmed breast cancer

• Primary and/or metastatic disease
• HER2 overexpression 3+ by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH)

• Tumors with HER2 2+ overexpression by IHC allowed if confirmed by FISH
• Progressive disease during or within 12 months of receiving prior regimen containing trastuzumab (Herceptin)
• Unidimensionally measurable disease

• At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
• The following are not considered measurable:

• Bone metastases
• Pleural or peritoneal effusion
• Ascites
• Leptomeningeal disease
• Lymphangitic disease
• Inflammatory breast cancer
• Cystic lesions
• CNS lesions
• CNS metastases allowed if all of the following conditions are met:

• Asymptomatic
• At least 3 months since prior surgery and/or cranial irradiation
• At least 3 weeks since prior steroids
• Hormone receptor status:

• Not specified
• Male or female
• Performance status - ECOG 0-2
• Granulocyte count at least 1,000/mm^3
• Platelet count at least 100,000/mm^3
• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• SGOT and SGPT no greater than 2 times ULN (5 times ULN for liver metastases)
• Alkaline phosphatase no greater than 2 times ULN (5 times ULN for liver metastases)
• Creatinine no greater than 1.5 times ULN
• LVEF at least lower limit of normal by MUGA or echocardiogram
• No congestive heart failure or active ischemic heart disease
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No psychiatric illness, medical condition, or uncontrolled infection that would preclude study
• No underlying immunodeficiency (e.g., HIV or autoimmune disease)
• No other prior malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
• See Disease Characteristics
• Prior cumulative doxorubicin dose no greater than 360 mg/m^2
• At least 3 weeks since prior chemotherapy
• No more than 2 prior chemotherapy regimens for metastatic disease
• No concurrent chemotherapy
• See Disease Characteristics
• At least 3 weeks since prior endocrine therapy
• No concurrent corticosteroids or dexamethasone
• Concurrent hormones allowed for conditions unrelated to disease (e.g., insulin for diabetes)
• See Disease Characteristics
• At least 3 weeks since prior radiotherapy
• No prior radiotherapy to study lesion, unless evidence of disease progression
• No concurrent palliative radiotherapy
• See Disease Characteristics
• At least 4 weeks since prior major surgery
• No concurrent immunosuppressive drugs