Phase II Trial of Anti-HER-2 Monoclonal Antibody Trastuzumab (Herceptin) in Combination With Low Dose Interleukin-2 (Proleukin) in Metastatic Breast Cancer Patients Who Have Previously Failed Trastuzumab
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.
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
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.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Response rate using Response Evaluation Criteria in Solid Tumors (RECIST)
Up to 12 months
Ohio State University
United States: Food and Drug Administration
|Ohio State University Medical Center||Columbus, Ohio 43210|