trastuzumab and interleukin-2 in treating patients with metastatic breast cancer

Conditions: HER2-positive Breast Cancer; Male Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer

Summary: monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. interleukin-2 may stimulate a person's white blood cells to kill breast cancer cells. phase ii trial to study the effectiveness of trastuzumab plus interleukin-2 in treating patients who have metastatic breast cancer that has not responded to previous trastuzumab therapy.

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.

Eligibility criteria:
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