Hepatic Arterial Infusion (HAI) With Floxuridine (FUDR) and Dexamethasone (Dex) Combined With Systemic Gemcitabine and Oxaliplatin in Patients With Unresectable Intrahepatic Cholangiocarcinoma (ICC)

Inclusion Criteria: * Age ≥ 21 years * Histologically confirmed intrahepatic cholangiocarcinoma (also variously reported as peripheral cholangiocarcinoma, cholangiolar carcinoma or cholangiocellular carcinoma) (ICC). Confirmation of the diagnosis at MSKCC or at the enrolling institution must be obtained prior to initiation of protocol therapy. * Clinical or radiographic evidence of metastatic disease to regional lymph nodes will be allowed, provided it is amenable to resection. * Radiographically measurable disease. Measurable disease is defined as disease that can be assessed with 2-dimensional measurements on a cross-sectional imaging. Minimum lesion size is 2cm in greatest diameter as per RECIST criteria. * Disease must be considered unresectable at the time of preoperative evaluation. * Presence of less than 70% liver involvement by cancer. * Patients may have failed ablative therapy * Patient previously treated with systemic chemotherapy will be eligible * KPS ≥ 60% and be considered candidates for general anesthesia, abdominal exploration and hepatic artery pump placement * Patients with chronic hepatitis and/or cirrhosis are eligible, but must be Child-Pugh class A * Patients must be able to read, understand and sign informed consent * WBC ≥ 2,000 cells/mm3 * Platelet count ≥ 75,000/mm3 * Creatinine ≤ 1.8 mg/dl * Total bilirubin \< 1.5 mg/dl Exclusion Criteria: * Presence of distant metastatic disease. Patients will undergo radiographic evaluation to exclude the possibility of distant metastatic disease. For patients who have undergone pre- or postoperative biopsies that definitively diagnose ICC, the diagnostic studies may be modified at the discretion of the MSKCC Principal Investigator. Clinical or radiographic evidence of metastatic disease to regional lymph nodes will be allowed, provided it is amenable to resection. * Prior treatment with FUDR * Prior external beam radiation therapy to the liver * Diagnosis of sclerosing cholangitis * Clinical evidence or portal hypertension (ascites, gastroesophageal varices, or portal vein thrombosis) surgically related ascites does not exclude the patient) * Active infection * Pregnant or lactating women * History of other malignancy within the past 3 years (except non-melanoma skin cancer) * Life expectancy less than 12 weeks * Inability to comply with study and/or followup procedures * History of peripheral neuropathy (Note: this does not apply to Cohort 3)