Second Line Therapy in Advanced Biliary Tract Cancer (BIT-2)

Inclusion Criteria:

1. Signed and dated IRB/IEC-approved Informed Consent.
2. Cytological or histological diagnosis of locally advanced or metastatic adenocarcinoma of the biliary tract (Ampulla of Vater, gallbladder, intra or extra-hepatic biliary ducts).
3. Disease progressing after first-line chemotherapy with gemcitabine and platinum analogs (only one prior systemic therapy allowed).
4. Age 18-75 years
5. Karnofsky Performance Status > 50%
6. Estimated life expectancy of at least 3 months.
7. Negative pregnancy test (if female in reproductive years).
8. 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
9. 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).
10. 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.
11. Able and willing to comply with scheduled visits, therapy plans, and laboratory tests required in this protocol.

Exclusion Criteria:

1. Previous or concurrent malignancies at other sites with the exception of surgically cured carcinoma in-site of the cervix and basal or squamous cell carcinoma of the skin and of other neoplasm without evidence of disease at least from 5 years.
2. Known brain metastases.
3. Previous second-line or adjuvant treatment.
4. Concurrent treatment with other experimental drugs.
5. Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, cardiac arrhythmia) ≤1 year prior to dosing.
6. Clinically significant disease including: Cerebral Vascular Accident; other serious underlying medical condition(s) which could impair the ability of the patient to participate in the study.
7. History of interstitial lung disease (eg, pneumonia or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest CT scan
8. Known positive tests for human immunodeficiency virus (HIV) infection, active hepatitis B or hepatitis C
9. Subject who is pregnant or breast feeding
10. Woman or man of child-bearing potential not consenting to use adequate contraceptive precautions ie. double barrier contraceptive methods (e.g., diaphragm plus condom), or abstinence during the course of the study and for 6 months after the last study drug administration for women, and 1 month for men
11. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule