Capecitabine, Vinorelbine, and Trastuzumab in Treating Patients With Metastatic Breast Cancer

OBJECTIVES:

Primary

• Determine the overall response rate in patients with HER2/neu-overexpressing metastatic breast cancer treated with first- or second-line therapy comprising capecitabine, vinorelbine, and trastuzumab (Herceptin^®).

Secondary

• Determine the time to disease progression, duration of response, and overall survival of patients treated with this regimen.
• Determine the safety profile of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral capecitabine twice daily on days 1-14, vinorelbine IV over 6-10 minutes on days 1 and 8, and trastuzumab (Herceptin^®) IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months until disease progression and then every 6 months for up to 5 years.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed invasive breast cancer

• Metastatic disease
• HER2/neu-positive by immunohistochemistry (3+ by HercepTest^™ or equivalent) OR positive for amplification by fluorescent in situ hybridization

• Testing may be performed in the primary tumor or the metastatic site
• Received prior anthracycline or taxane as adjuvant therapy or for metastatic disease
• Measurable disease

• At least one measurable lesion ≥ 2.0 cm by CT scan or MRI OR ≥ 1.0 cm by spiral CT scan
• The following are considered non-measurable disease:

• Bone lesions
• Leptomeningeal disease
• Ascites
• Pleural/pericardial effusion
• Inflammatory breast disease
• Lymphangitis cutis/pulmonis
• Abdominal masses that are not confirmed and followed by imaging techniques
• Cystic lesions
• No bone metastases as the only evidence of metastasis
• Previously treated CNS metastases allowed provided disease has been stable for ≥ the past 3 months
• Hormone receptor status:

• Not specified

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Female or male

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Hemoglobin ≥ 8.0 g/dL
• Platelet count ≥ 100,000/mm^3
• No known uncontrolled coagulopathy

Hepatic

• Bilirubin ≤ 3.0 times the upper limit of normal (ULN)
• One of the following must be true:

• AST or ALT ≤ 5 times ULN AND alkaline phosphatase normal
• Alkaline phosphatase ≤ 5 times ULN AND AST or ALT normal
• Alkaline phosphatase ≤ 2.5 times ULN AND AST or ALT ≤ 1.5 times ULN
• INR ≤ 1.5 times ULN

Renal

• Calcium ≤ 11.5 mg/dL
• Creatinine ≤ 1.5 times ULN
• Creatinine clearance ≥ 30 mL/min

Cardiovascular

• LVEF ≥ 50% by MUGA or echocardiogram
• No clinically significant (i.e., active) cardiac disease
• No congestive heart failure
• No symptomatic coronary artery disease
• No myocardial infarction within the past 12 months
• No cardiac arrhythmia not controlled with medication

Gastrointestinal

• Able to take oral medication
• No lack of physical integrity of the upper gastrointestinal tract
• No clinically significant malabsorption syndrome

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 30 days after study participation
• No history of allergy or hypersensitivity to study drugs, drug product excipients, including polysorbate 80, or chemically similar agents
• No prior unanticipated severe reaction to fluoropyrimidine therapy
• No know hypersensitivity to fluorouracil
• No known dihydropyrimidine dehydrogenase deficiency
• No history of uncontrolled seizures or CNS disorders
• No clinically significant psychiatric disability that would preclude giving informed consent or study compliance
• No other serious uncontrolled infection or disease
• No other malignancy within the past 5 years except cured basal cell skin cancer, carcinoma in situ of the cervix, or contralateral breast cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Prior adjuvant trastuzumab (Herceptin^®) allowed as adjuvant or first-line therapy for metastatic disease
• No concurrent immunotherapy

Chemotherapy

• See Disease Characteristics
• No more than 1 prior chemotherapy regimen in the advanced or metastatic (non-adjuvant) setting
• No prior continuous (≥ 24 hours) fluorouracil infusion
• No prior capecitabine
• No prior oral fluoropyrimidines (e.g., eniluracil and fluorouracil, uracil and tegafur, S1, or emitefur)

Endocrine therapy

• At least 1 day since prior hormonal therapy
• No concurrent hormonal therapy

Radiotherapy

• More than 4 weeks since prior radiotherapy to the axial skeleton (i.e., skull, spinal column, sternum, or ribs)
• No concurrent radiotherapy

Surgery

• More than 4 weeks since prior major surgery
• No prior organ allografts requiring immunosuppressive therapy

Other

• More than 4 weeks since prior investigational drugs
• No concurrent sorivudine or its chemically related analogues (e.g., brivudine)
• No concurrent allopurinol, metronidazole, or cimetidine
• No other concurrent cytotoxic agents
• No other concurrent investigational drugs
• No other concurrent anticancer therapy