A Randomized Phase II Study of Systemic Chemotherapy With or Without HAI FUDR/Dexamethasone in Patients With Unresectable Intrahepatic Cholangiocarcinoma

Inclusion Criteria: * Age ≥18 years * ECOG 0-1 * Histologically confirmed intrahepatic cholangiocarcinoma (also variously reported as peripheral cholangiocarcinoma, cholangiolar carcinoma or cholangiocellular carcinoma) (IHC). Confirmation of the diagnosis at MSKCC or at the enrolling institution must be obtained prior to randomization. * Clinical or radiographic evidence of metastatic disease confined to the liver. Note: presence of regional (porta hepatis) lymph node metastases will be allowed, provided they are amenable to resection. (Note: If peritoneal or other extrahepatic disease is found at time of pump placement, the pump will not be implanted. The patient will be removed from study, deemed nonevaluable and will not count toward the overall study accrual.) * 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 2 cm in greatest diameter as per RECIST criteria. * Disease must be considered unresectable at the time of preoperative evaluation.\* * Considered candidate 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. * WBC ≥ 2,000/mcL , ANC ≥ 1000/mcL * Platelet count ≥ 75,000/mcL * Creatinine ≤ 1.8 mg/dL * Total bilirubin \< 1.5 mg/dL * Hgb \> 7 g/dL The % involvement of the liver will be determined by radiologists after review of imaging 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 post-operative biopsies that definitively diagnose IHC, 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. * Patients previously treated with systemic chemotherapy for IHC will be non-eligible. * Prior treatment with FUDR. * Prior external beam radiation therapy to the liver. * Prior ablative 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 within one week prior to HAI placement. * Pregnant or lactating women. * History of other malignancy within the past 3 years except with early stage/localized cancer that was surgically resected or radiation treatment that would yield the same result as surgery within the past 3 years. * Life expectancy \<12 weeks. * Inability to comply with study and/or follow-up procedures. * History of peripheral neuropathy. There is no exclusion of patients based on sex, ethnicity or race. For these reasons, the study results are expected to be generalizable to the Medicare beneficiary population.