Clinical trial NCT00442637 (phase 3, status: unknown status)
Conditions: colorectal cancer metastatic
ICD codes: C05.2, C10.0, C16.0, C16.4, C17.0, C17.1, C17.2
Drugs: capecitabine + bevacizumab
SMILES: CCCCCOC(=O)NC1=NC(=O)N(C=C1F)[C@@H]1O[C@H](C)[C@@H](O)[C@H]1O
Eligibility criteria:

        Before the start of induction therapy:

        Inclusion Criteria:

          -  Histological proof of colorectal cancer (in case of a single metastasis, histological
             or cytological proof of this lesion should be obtained);

          -  Distant metastases (patients with only local recurrence are not eligible);

          -  Unidimensionally measurable disease (> 1 cm on spiral CT scan or > 2 cm on chest
             X-ray; liver ultrasound is not allowed). Serum CEA may not be used as a parameter for
             disease evaluation;

          -  In case of previous radiotherapy, at least one measurable lesion should be located
             outside the irradiated field.

          -  Ongoing or planned first line treatment with 6 cycles of Xeloda, Eloxatin, and
             Avastin.

        Exclusion criteria

          -  Prior adjuvant treatment for stage II/III colorectal cancer ending within 6 months
             before the start of induction treatment

          -  Any prior adjuvant treatment after resection of distant metastases

          -  Previous systemic treatment for advanced disease

        At randomisation:

        Inclusion criteria:

          -  WHO performance status 0-1 (Karnofsky PS > 70%);

          -  Disease evaluation with proven SD, PR or CR according to RECIST after 6 cycles of MTD
             chemotherapy performed in week 3-4 of the 6th cycle induction therapy, and
             randomisation performed in week 3-5 of the 6th cycle (see time table);

          -  Laboratory values obtained ≤ 2 weeks prior to randomisation: adequate bone marrow
             function (Hb > 6.0 mmol/L, absolute neutrophil count > 1.5 x 109/L, platelets > 100 x
             109/L), renal function (serum creatinine ≤ 1.5x ULN and creatinine clearance, Cockroft
             formula, > 30 ml/min), liver function (serum bilirubin ≤ 2 x ULN, serum transaminases
             ≤ 3 x ULN without presence of liver metastases or ≤ 5x ULN with presence of liver
             metastases);

          -  Life expectancy > 12 weeks;

          -  Age >= 18 yrs;

          -  Negative pregnancy test in women with childbearing potential;

          -  Expected adequacy of follow-up;

          -  Institutional Review Board approval;

          -  Written informed consent Exclusion criteria

          -  History or clinical signs/symptoms of CNS metastases;

          -  History of a second malignancy ≤ 5 years with the exception of adequately treated
             carcinoma of cervix or basal/squamous cell carcinoma of skin;

          -  Previous intolerance of XelodaR, EloxatinR, and/or AvastinR for which any of these
             drugs have been permanently discontinued; patients with previous dose reductions or
             delays are eligible; patients with grade 2 neurotoxicity after the 6th cycle are
             eligible, and retreatment with EloxatinR after PFS1 should depend on the grade of
             neurotoxicity at that moment;

          -  Known dihydropyrimidine dehydrogenase (DPD) deficiency;

          -  (Planned) radical resection of all metastatic disease;

          -  Uncontrolled hypertension, i.e. consistently > 150/100 mmHg;

          -  Use of more than 3 antihypertensive drugs;

          -  Significant cardiovascular disease < 1 yr before randomisation (symptomatic congestive
             heart failure, myocardial ischemia or infarction, unstable angina pectoris, serious
             uncontrolled cardiac arrhythmia, arterial thrombosis, cerebrovascular event, pulmonary
             embolism);

          -  Any of these significant cardiovascular events during previous fluoropyrimidine
             therapy;

          -  Chronic active infection;

          -  Any other concurrent severe or uncontrolled disease preventing the safe administration
             of study drugs;

          -  Any impairment of gastrointestinal function or -disease that may significantly impair
             the absorption of oral drugs (i.e. uncontrolled nausea, vomiting, diarrhoea (defined
             as >CTC grade 2), malabsorption syndrome, bowel obstruction, or inability to swallow
             tablets);

          -  Concomitant treatments: concomitant (or within 4 weeks before randomisation)
             administration of any other experimental drug under investigation; concurrent
             treatment with any other anti-cancer therapy; full-dose anticoagulation (is allowed if
             started during induction therapy);

          -  Continuous use of immunosuppressive agents (except the use of corticosteroids as
             anti-emetic prophylaxis/treatment).