A Multicenter Phase II Study to Determine the Efficacy of Capecitabine as First Line Monochemotherapy in Patients With HER2 Negative, Medium-risk, Metastatic Breast Cancer
1. Written informed consent prior to beginning specific protocol procedures, including
expected cooperation of the patients for the treatment and follow-up, must be
obtained and documented according to the local regulatory requirements.
2. Histologically confirmed carcinoma of the breast.
3. Negative for HER2-overexpression of the primary and/or metastatic tumour tissue
detected by immunohistochemistry (DAKO 0-2) or genamplification detected by FISH.
4. Locally advanced or metastatic stage of disease not suitable for surgery or
5. The following previous systemic treatment are eligible:
adjuvant chemotherapy (except if capecitabine was included) adjuvant endocrine
therapy palliative endocrine treatments treatment with bisphosphonates (adjuvant
and/or palliative) treatment with immunotherapies (adjuvant and/or palliative)
6. Patients must have either measurable or nonmeasurable target lesions according to the
WHO criteria (see Appendix 5).
7. At least 4 weeks since radiotherapy, with full recovery. The measurable disease must
be completely outside the radiation portal or there must be pathologic proof of
8. Complete radiology and tumor measurement work up within 4 weeks prior to
9. Karnofsky performance status evaluation > or = 60%
10. Age >18 years
11. WBC > or = 3000 cells/microl, platelet count > or = 100,000 cells/microl.
12. Bilirubin < or = 2x the upper limit of normal for the institution (ULN); elevation of
transaminases and alkaline phosphatase < 2.5x ULN or <5x ULN for patients with liver
13. Creatinine < or = 1,25 x upper normal value or creatinin-clearance > 50 ml/min
(according to Cockroft Gault).
14. If of childbearing potential, negative pregnancy test. In addition the patient has to
agree to use an effective method to avoid pregnancy for the duration of the study.
15. Female and male patients
1. Known hypersensitivity reaction to the compounds or incorporated substances or known
dihydropyrimidine dehydrogenase deficiency.
2. Concurrent immunotherapy or hormonal therapy (antihormonal, contraceptive and/or
replacement therapy). Bisphosphonates may be continued.
3. Parenchymal brain metastases, unless adequately controlled by surgery and/or
radiotherapy with complete resolution of symptoms and discontinuation of all
4. Life expectancy of less than 3 months.
5. Serious intercurrent medical or psychiatric illness that may interfere with the
planned treatment (including AIDS and serious active infection).
6. History of other malignancy within the last 5 years which could affect the diagnosis
or assessment of metastatic breast cancer.
7. Patients with indication for polychemotherapy.
8. Concurrent treatment with other experimental drugs. Participation in another clinical
trial with any investigational not marketed drug within 30 days prior to study entry.
9. Treatment with sorivudine or derivates e.g. brivudin.
10. Pregnant or nursing women.