['cholangiocarcinoma']
['folfirinox']

        Inclusion Criteria:

          -  Histological or cytological diagnosis of cholangiocarcinoma.

          -  Metastatic disease or irresectable locally advanced cholangiocarcinoma.

          -  Measurable disease according RECIST criteria version 1.1.

          -  Age from 18 to 75 year.

          -  WHO/ECOG performance status 0-2.

          -  Patients who received at least 3 cycles of gemcitabine/cisplatin in the first line.

          -  Adequate hematological function (WBC > 3.0 x 109/L, platelets > 100 x109/L)

          -  Adequate hepatic function (bilirubin ≤ 1.5 x upper normal limit (ULN); ALAT or ASAT
             <5x ULN in case of liver metastases and < 2.5 x ULN in absence of liver metastases.

          -  Adequate renal function (creatinine clearance > 60 ml/min; creatinine <120 µmol/L)

          -  Absence of cardiac insufficiency, chest pain (not medically controlled) and myocardial
             infarction in the 12 months preceding study entry.

          -  Signed informed consent.

        Exclusion Criteria:

          -  Concurrent secondary malignancies or other malignancies within 3 years prior to enter
             this study with the exception of non-metastatic basal cell or squamous cell skin
             cancer or carcinoma in situ of the cervix treated by cone-biopsy or resection

          -  Presence of cerebral or meningeal metastases

          -  Contraindication to any of the substances of the planned treatment.

          -  History of chronic diarrhea or colorectal inflammatory conditions, or of unresolved
             occlusion or sub-occlusion for which symptomatic treatment is being administered

          -  Active infection or other serious underlying conditions which may prevent the patient
             from receiving the planned treatment. For example: prolonged unresolved bacterial
             cholangitis with destruction of bile duct branches (e.g. after endoprosthesis
             insertion) or two or more cholangitis in the last 6 months. Patients with other active
             or uncontrolled severe infection, cirrhosis or chronic active hepatitis will be
             excluded.

          -  Presence of cardiac insufficiency, unstable angina pectoris, symptomatic congestive
             heart, failure myocardial infarction 6 months prior to randomization, serious
             uncontrolled cardiac arrhythmia.

          -  Inclusion in another investigational clinical trial

          -  Women who are pregnant, breast-feeding or not using adequate contraceptive

          -  Age younger than 18 or older than 76 years

          -  Individuals under correctional supervision or guardianship
      