Trastuzumab and Irinotecan in Treating Patients With HER2/Neu Positive Metastatic Breast Cancer

OBJECTIVES:

Primary

• Determine the overall objective response-rate (partial and complete) and stable disease rate in patients with HER2/neu positive metastatic breast cancer treated with the combination of irinotecan hydrochloride and trastuzumab (Herceptin®) after prior first- or second-line therapy with trastuzumab combined with other chemotherapeutic agents.

Secondary

• Determine the toxicities of this combination regimen.
• Determine the duration of response and time to disease progression in patients treated with this combination.
• Document development of brain metastases or progression of known metastases in patients treated with this regimen.

OUTLINE: Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on days 1, 8, 15, and 22 and irinotecan hydrochloride IV over 30-60 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed metastatic breast carcinoma
• Received 1-3 prior chemotherapy regimens for metastatic disease

• Documented progressive disease
• Repeated courses of the same chemotherapy agent alone or in combination are considered a single regimen
• Prior trastuzumab (Herceptin®) alone or with chemotherapy allowed

• Other biologic agents are not considered a chemotherapy regimen
• Measurable disease

• Patients with bone-only disease who are evaluable by tumor markers (e.g., CA15-3, CEA, or CA27.29) are eligible

• Patients must have prior evidence of correlation of disease activity with changes in tumor marker level
• Confirmation of HER2/neu status by a positive test for gene amplification by fluorescence in situ hybridization or 3+ by immunohistochemistry
• Brain metastases allowed if the following criteria are met:

• Brain metastases were previously treated and are currently stable as documented by head CT scan with contrast or MRI within 4 weeks of study entry

• Patients with existing brain metastases should have stability documented by prior imaging ≥ 8 weeks before the baseline scan
• Hormone-receptor status not specified

PATIENT CHARACTERISTICS:

• Menopausal status not specified
• ECOG performance status ≤ 2
• Absolute neutrophil count ≥ 1,000/mm^3
• Platelet count ≥ 100,000/mm^3
• Life expectancy ≥ 12 weeks
• No history of congestive heart failure
• Documented ejection fraction ≥ 45% by MUGA scan or echocardiogram within 1 month of study entry
• Total bilirubin < 3 times upper limit of normal (ULN)
• AST < 3 times ULN (5 times ULN if due to liver involvement)
• Creatinine < 1.5 times ULN
• No history of serious adverse events related to trastuzumab
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No severe, concurrent illness that would prevent compliance with study protocol
• No chronic severe diarrheal illness
• No history of Gilbert's disease or known deficiency in glucuronidation
• No recent or current history of alcoholism or acute viral hepatitis

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No chemotherapy or hormonal therapy within the past 2 weeks
• Prior or concurrent bisphosphonates allowed
• No prior irinotecan (other camptothecins allowed)
• No concurrent radiotherapy
• No ongoing treatment with any other investigational agent