Phase II Study of Capecitabine in Combination With Vinorelbine and Trastuzumab for the First- or Second-LineTreatment of HER2+ Metastatic Breast Cancer

Inclusion Criteria

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

Menopausal status

- Not specified

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