Second Line Therapy for Advanced Intrahepatic Cholangiocarcinoma

Inclusion Criteria:

* Signed and dated IRB/IEC-approved Informed Consent.
* Cytological or histological diagnosis of locally advanced or metastatic adenocarcinoma of the Intrahepatic Cholangiocarcinoma.
* Disease progressing after first-line chemotherapy with gemcitabine and platinum analogs (only one prior systemic therapy allowed).
* Age 18-75 years
* Karnofsky Performance Status \> 50%
* Estimated life expectancy of at least 3 months.
* Negative pregnancy test (if female in reproductive years).
* Adequate bone marrow, liver and kidney function: leukocyte \> 3500/mm3; absolute neutrophil count (ANC) \> 1500/mm3; platelet count \> 100000/mm3; hemoglobin \> 10 g/dl; creatinine \< 1.5 mg/dL; total bilirubin ≤ 1.5 x upper limit of normal range (ULN); SGOT e SGPT ≤ 2.5 ULN
* At the time of start of treatment, at least 2 weeks must have elapsed since completion of prior chemotherapy, minor surgery and radiotherapy (provided that no more than 25% of bone marrow reserve has been irradiated).
* Resolution of all acute toxic effects of any prior chemotherapy, surgery or radiotherapy to NCI CTC (Version 4.03) grade ≤ 1 for hematologic toxicities and ≤ 2 for non hematologic toxicities, with the exception of alopecia.
* Able and willing to comply with scheduled visits, therapy plans, and laboratory tests required in this protocol.

Exclusion Criteria:

* History of cardiac disease
* Ongoing infection \> Grade 2 according to NCI-CTCAE version 4.03. Hepatitis B is allowed if no active replication (defined as abnormal ALT \>2xULN associated with HBV DNA \>20,000 IU/mL) is present
* Severe co-morbid illness and/or active infections including active hepatitis C and human immunodeficiency virus (HIV) infection
* History of interstitial lung disease (ILD).
* Any cancer curatively treated \< 3 years prior to study entry, except cervical carcinoma in situ, treated basal cell carcinoma, and superficial bladder tumors (Staging: Ta, Tis and T1).
* Renal failure requiring hemo- or peritoneal dialysis.
* Clinically significant GI bleeding (CTCAE 4.03 grade 3 or higher) within 30 days prior to start of screening
* Thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks) within 6 months prior to start of screening.
* History of organ allograft, cornea transplantation will be allowed
* Active CNS metastases not controllable with radiotherapy or corticosteroids Visible retinal pathology as assessed by ophthalmologic exam that is considered a risk factor for RVO or CSR.
* Known history of hypersensitivity to study drugs
* Non-healing wound, ulcer, or bone fracture.
* Patients with seizure disorder requiring medication.
* Acute steroid therapy or taper for any purpose (chronic steroid therapy is acceptable provided that the dose is stable for 1 month before start of screening and thereafter).
* Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
* Pregnant or lactating women. Women of childbearing potential not employing adequate contraception. Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to start of study treatment and a negative result must be documented before first dose of study drug.