RATIONALE: Drugs used in chemotherapy, such as capecitabine and vinorelbine, work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor killing substances to them without harming normal cells. Combining capecitabine and vinorelbine with trastuzumab may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining capecitabine and vinorelbine with trastuzumab in treating patients who have metastatic breast cancer.

Condition	Treatment or Intervention	Phase
recurrent breast cancer stage IV breast cancer Male Breast Cancer	Drug: capecitabine  Drug: trastuzumab  Drug: vinorelbine  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: monoclonal antibody therapy	Phase II

OBJECTIVES: Primary

• Determine the overall response rate in patients with HER2/neu-overexpressing metastatic breast cancer treated with first-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.

PROJECTED ACCRUAL: A total of 5-47 patients will be accrued for this study within 23 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

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
• Disease progression after prior adjuvant or neoadjuvant taxane-based therapy
• 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
• No known CNS metastases
• 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
• PT normal

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
• No concurrent immunotherapy

Chemotherapy

• See Disease Characteristics
• No prior chemotherapy in the 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
• 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 participation in an investigational drug study
• No concurrent sorivudine or its chemically related analogues (e.g., brivudine)
• No other concurrent cytotoxic agents
• No other concurrent investigational drugs
• No other concurrent anticancer therapy

Study chairs or principal investigators

Winston Tan, MD,  Study Chair,  Mayo Clinic - Jacksonville   
Muhammad Salim, MD,  Allan Blair Cancer Centre at Pasqua Hospital   
Edith A. Perez, MD,  Mayo Clinic - Jacksonville   

Study ID Numbers:  CDR0000390344; NCCTG-N0337
Record last reviewed:  September 2004
Record first received:  October 6, 2004
ClinicalTrials.gov Identifier:  NCT00093808
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-10-20