Clinical trial NCT01200212 (phase 3, status: terminated)
Conditions: breast cancer
ICD codes: C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60
Drugs: taxane, avastin, taxane, avastin, xeloda
SMILES: CCCCCOC(=O)NC1=NC(=O)N(C=C1F)[C@@H]1O[C@H](C)[C@@H](O)[C@H]1O
Reason stopped: 
    a planed interim analysis shows no benefits, but higher adverse event rates for the
    experimental arm.
  
Eligibility criteria:

        Inclusion Criteria:

          -  ECOG performance status 0-2

          -  Histological confirmed carcinoma of the breast with no over expression of HER2

          -  Locally advanced or metastatic stage of disease not suitable for surgery or
             radiotherapy alone

          -  Patients must have either measurable or non-measurable target lesions according to
             RECIST criteria (phase III). Complete staging work-up within 4 weeks prior to
             registration. All patients must have chest X-ray (PA and lateral), abdominal
             ultrasound or CT scan or MRI, and bone scan. In case of positive bone scan, bone X-ray
             is mandatory. Other tests may be per- formed as clinically indicated

          -  The following previous systemic treatment are eligible:

          -  (neo)adjuvant chemotherapy (except if capecitabine was included) However if
             (neo)adjuvant chemotherapy was anthracycline based, the maximum cumulative dose of
             prior anthracycline therapy must not exceed 360 mg/m2 for doxorubicin and 720 mg/m2
             for epirubicin. If taxanes or capecitabine were part of (neo)adjuvant treatment, a
             treatment-free interval of > 6 months is requested

          -  adjuvant endocrine therapy.

          -  palliative endocrine treatments

          -  treatment with bisphosphonates

          -  treatment with immunotherapies

          -  Patient has to be fully recovered from previous radiotherapy. At least one measurable
             lesion must be completely outside the radiation field or there must be pathologic
             proof of progressive disease

          -  Absolute neutrophil count ≥ 2000 cells/ul, platelet count ≥ 100,000 cells/ul.

          -  Bilirubin ≤ 1.5x 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
             metastases

          -  Creatinine ≤ 1,25x ULN or creatinin-clearance > 50 ml/min (according to Cockroft
             Gault). Urine dipstick for proteinuria <2+. Patients discovered to have ≥2+
             proteinuria on dipstick urinalysis should undergo a 24 hour urine collection and must
             demonstrate ≤1 g of protein in 24 hours

          -  Negative pregnancy test (urine or serum) within 14 days prior to registration for all
             women of childbearing potential

          -  Patients must be available and compliant for treatment and follow-up. Patients
             registered on this trial must be treated and followed up at the participating or a
             cooperating site

        Exclusion Criteria:

          -  Known hypersensitivity reaction to the compounds or incorporated substances or known
             dihydropyrimidine dehydrogenase deficiency

          -  Previous chemotherapy for metastatic disease, concurrent immunotherapy or hormonal
             therapy (antihormonal, contraceptive and/or replacement therapy). Bisphosphonates may
             be continued

          -  Life expectancy of less than 3 months

          -  Serious intercurrent medical or psychiatric illness that may interfere with the
             planned treatment (including AIDS and serious active infection).

          -  Known or suspected congestive heart failure (>NYHA I) and/or coronary heart disease,
             angina pectoris requiring antianginal medication, previous history of myocardial
             infarction, evidence of transmural infarction on ECG, un- or poorly controlled
             arterial hypertension (i.e. BP >150/100 mmHg under treatment with two antihypertensive
             drugs), rhythm abnormalities requiring permanent treatment, clinically significant
             valvular heart disease-

          -  Currently active infection

          -  Active peptic ulcer, incomplete wound healing or unhealed bone fracture

          -  Previous thromboembolic events, known hemorrhagic diathesis, coagulopathy with
             increased bleeding risk, or treatment with anticoagulants Current or recent (within 10
             days of first dose of bevacizumab) use of acetylic acid (>325mg/day) or clopidogrel (>
             75mg/day)

          -  Disease significantly affecting gastrointestinal function, e.g. mal- absorption
             syndrome, resection of the stomach or small bowel, ulcerative colitis; abdominal
             fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of
             enrolment

          -  Major surgery within the last 28 days or anticipation of the need for major surgery
             during study treatment with bevacizumab. No minor surgeries including insertion of an
             indwelling catheter within 24 h prior to randomization

          -  Parenchymal brain metastases, unless adequately controlled by surgery and/or
             radiotherapy with complete resolution of symptoms and discontinuation of all steroids

          -  History of other malignancy within the last 5 years which could affect the diagnosis
             or assessment or outcome of metastatic breast cancer

          -  Concurrent treatment with other experimental drugs; participation in another clinical
             trial with any investigational drug within 30 days prior to study entry

          -  Treatment with sorivudine or derivates e.g. brivudine

          -  Pregnant or lactating patients. Patients of childbearing potential must implement
             adequate non-hormonal contraceptive measures (barrier methods, intra uterine
             contraceptive devices, sterilization) during study treatment