A Trial of Systemic Chemotherapy in Combination With Conventional Transarterial Chemoembolization in Patients With Advanced Intra-Hepatic Cholangiocarcinoma

Inclusion Criteria: * Patient is at least 18 years of age. * Patient has advanced, unresectable intrahepatic cholangiocarcinoma (ICC). Advanced, unresectable ICC is defined as biopsy-confirmed adenocarcinoma in the liver, with an immunohistochemical profile consistent with a pancreatico-biliary primary, not involving the common bile duct or bifurcation, and not amenable to surgical resection. * Eligible for conventional TACE as defined by local treatment guidelines. * Child-Pugh class of A to B7. * Adequate end-organ and bone marrow function as manifested as: * Hemoglobin ≥ 9 g/dL * Absolute neutrophil count ≥ 1500/mm3 * Creatinine ≤ 2.0 g/dL * AST and ALT ≤ 5 x ULN * Albumin ≥ 2.4 mg/dL * Total bilirubin ≤ 2.5 mg/dL * Platelets ≥ 100,000/mm3 * For TACE procedures, subjects are allowed to have platelets ≥ 75,000/mm3. * Disease is liver-dominant with \>70% of measurable disease burden within the hepatic parenchyma. * No prior surgery or chemotherapy for ICC. * ECOG performance status of 0-1. * No other active malignancy within 2 years. * Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of the study. * Ability to understand and willingness to sign a written informed consent document. Exclusion Criteria: * Prior or concurrent chemotherapy treatment for advanced ICC. * History of allergic reactions attributed to compounds of similar chemical or biological composition to gemcitabine, cisplatin, doxorubicin, or mitomycin-C. * Active treatment with CYP3A4 strong inhibitors or inducers. * Recent surgical procedure within 21 days of study enrollment. * Severe and/or uncontrolled co-morbid medical conditions including, but not limited to, active infection, viral hepatitis, congestive heart failure, cardiac arrhythmia, unstable angina pectoris, and psychiatric illness or social circumstance that would limit compliance with study requirements. * Pregnancy during study duration. * Active immunosuppressive medications. * Presence of grade 2 or higher hepatic encephalopathy. * Complete occlusion of the entire portal venous system. Partial or branch portal vein occlusion allowed if without reversal of flow. * Radiotherapy within 21 days from treatment with study interventions or medications. * Current, recent (within 4 weeks of first infusion of this study), or planned participation in additional experimental drug. * Unstable angina. * New York Heart Association (NYHA) Grade II or greater congestive heart failure (Appendix C). * History of myocardial infarction or CVA within 6 months prior to study enrollment. * Clinically significant peripheral vascular disease. * Inability to comply with study and/or follow-up procedures. * Life expectancy of less than 12 weeks.