Inclusion Criteria:

1. Written informed consent given according to ICH/GCP, and local regulation.

2. Histologically or cytologically proven intrahepatic cholangiocarcinoma.

3. Disease that is not amenable to surgery, radiation, or combined modality therapy with
curative intent.

4. Gemcitabine with or without platinum pre-treated patients with documented progression

5. Local, locally-advanced or metastatic disease documented as having shown progression
on a scan (CT, MRI).

6. Measurable tumor according to RECIST criteria with at least one unidimensionally
measurable target lesion

7. No evidence of biliary duct obstruction unless obstruction controlled by local
treatment or, in whom the biliary tree can be decompressed by endoscopic or
percutaneous stenting with subsequent reduction in bilirubin £ 1.5xULN.

8. Age between 18 and 80 years old

9. Eastern Cooperative Oncology Group (ECOG) Performance Status :0-1

10. Life expectancy ≥ 3 months.

11. Ability to swallow oral compound.

12. No acute toxic effects of previous treatment superior to grade to 1.

13. Laboratory requirements:

Hematologic: absolute neutrophil count (ANC) 1.5 x 103/mm3, platelets 100 x 103/mm3,
hemoglobin 9 g/dl and Hepatic: Bilirubin < 1.5 x upper normal limit (ULN), and
alkaline phosphatase (AP)2.5 xULN. AST and ALT may be 5 x ULN Patients with jaundice
Serum amylase and lipase 1.0 x ULN Prothrombin time and partial thromboplastin time
1.7 xULN, serum albumin 2.8 g/dl. Renal: Serum creatinine 1.5 xULN , and clearance >
60 ml/min.

14. Normal cardiovascular function

15. Adequate organ function

16. No cardiovascular events during the year prior to study entry

17. Female patients must be surgically sterile or postmenopausal, or must agree to use
effective contraception during the period of therapy. All female patients with
reproductive potential must have a negative pregnancy test (serum or urine) within 7
days prior to starting study drug. Male patients must be surgically sterile or must
agree to use effective contraception during the period of therapy. The definition of
effective contraception will be based on the judgment of the investigator or a
designated associate

18. Absence of any psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol and follow-up schedule;
those conditions should be discussed with the patient before registration in the
trial

19. Willingness and ability to comply with scheduled visits, treatment plans, laboratory
tests and other study procedures

20. Registration in a national health care system (CMU included).

Exclusion Criteria:

1. Hilar cholangiocarcinomas, cholangiocarcinomas located in the gall bladder, hepatic
capsule effraction, extrahepatic primary cholangiocarcinoma, carcinoma of the Water
ampullum.

2. Prior treatment with other chemotherapy than gemcitabine and/or platinum.

3. Concomitant treatment with any chemotherapy, chemoembolization therapy,
immunotherapy, antitumoral hormonotherapy or investigational anticancer agents..

4. Prior treatment with any tyrosine kinase inhibitors or anti-VEGF angiogenic
inhibitors.

5. Diagnosis of any second malignancy within the last 5 years, except for adequately
treated basal cell or squamous cell skin cancer, or in situ carcinoma of the cervix
uteri.

6. Treatment with potent CYP3A4 inhibitors and inducers within 7 and 12 days,
respectively prior to study drug administration.

7. Pre-existing thyroid abnormality of thyroid function that cannot be maintained in the
normal range with medication.

8. Concomitant treatment with therapeutic doses of anticoagulants (low dose warfarin
(Coumadin) up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed).

9. Unstable systemic diseases including uncontrolled hypertension (>150/100 mmHg despite
optimal medical therapy) or active uncontrolled infections.

10. Drug having proarrhythmic potential (terfenadine, quinidine,procainamide,
disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide and
flecainide).

11. Any of the following within the 12 months prior to study drug administration:
myocardial infarction, severe/unstable angina, symptomatic congestive heart failure,
cerebrovascular accident or transient ischemic attack, or pulmonary embolism.

12. Abnormal cardiac function with abnormal 12 lead ECG. Ongoing cardiac dysrhythmias of
NCI CTC grade2, atrial fibrillation of any grade, or prolongation of the QTc interval
to >450 msec for males or >470 msec for females.

13. Symptomatic brain metastases, spinal cord compression, or new evidence of brain or
leptomeningeal disease.

14. Current treatment with any other investigational medicinal product.

15. Positive test for human immunodeficiency virus (HIV) or acquired immunodeficiency
syndrome (AIDS) related illness

16. Pregnancy or breastfeeding.

17. Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or study
drug administration, or may interfere with the interpretation of study results, and
in the judgment of the investigator would make the patient inappropriate for entry
into this study.