Capecitabine, Vinorelbine, and Trastuzumab in Treating Patients With Metastatic Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: trastuzumab; capecitabine; vinorelbine tartrate
Intervention MeSH terms: Capecitabine; Trastuzumab; Vinorelbine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 47.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: recurrent breast cancer; stage IV breast cancer; male breast cancer

Summary:

      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. Giving capecitabine and vinorelbine
      together with trastuzumab may kill more tumor cells.

      PURPOSE: This phase II trial is studying how well giving capecitabine and vinorelbine
      together with trastuzumab works in treating patients who have metastatic breast cancer.
    

Eligibility 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

        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