Enrollment closed by internal scientific review committee due to slow accrual.

The purpose of this study is to determine the safety and maximum tolerated dose (MTD) of 90 Y TARE (Y90) in combination with gemcitabine and cisplatin in patients with unresectable intrahepatic cholangiocarcinoma (ICC).

Gemcitabine and cisplatin chemotherapy is the current standard for the treatment of unresectable intrahepatic cholangiocarcinoma. 90Y TARE combined with the current standard may be an ideal way to improve disease control in the liver as almost all patients die from their disease in the liver. The data from this trial would then be used to move to a phase II trial to determine efficacy to see if a phase III trial would be warranted. In addition, assessment of the molecular classification of intrahepatic cholangiocarcinoma could determine if there is difference in survival with chemotherapy and 90Y TARE. Finally, MRI before and after treatment will be used to determine if utilizing the percent increase of mean ADC correlates with survival.

Inclusion Criteria:

• Histologic Documentation: Core needle biopsy or surgical specimen that confirms intrahepatic cholangiocarcinoma (ICC). Patients must be determined to be unresectable by a multidisciplinary team that includes a hepatobiliary surgeon.
• No prior liver radiation therapy or immunotherapy for cholangiocarcinoma.
• Only one previous single agent chemotherapy for ICC allowed.
• Patient may have prior liver resection.
• Age > 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status < 2 (see Appendix E)
• Child's Pugh score of A (see Appendix F)
• Life expectancy of greater than 4 months
• Normal organ and marrow function as outlined in the protocol.
• Willingness to use effective contraceptive methods during the study. Patient may participate in the female (or female partner of male subject), either is not of childbearing potential (defined as postmenopausal for > 1 year or surgically sterile) or is practicing two forms of contraception. Sexually active male participants must agree to use a physical barrier method (male latex rubber condom with or without spermicide).
• Patients with well controlled HIV infection are eligible if their CD4 count is >499/cu mm and viral load is < 50 copies/ml.
• Pre-certification for the 90Y TARE should be performed prior to enrollment on this study.
• All patients must be informed of the investigational nature of this study and must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Patients who have had major surgery within 4 weeks prior to entering the study or those who have not recovered from complications from a surgery more than 4 weeks earlier.
• Patients may not be receiving any other investigational agents.
• Patients must not have any grade III/IV cardiac disease as defined by the New York Heart Association (NYHA) Criteria
• Patients must NOT have liver disease such as cirrhosis or sever hepatic impairment as defined by Child-Pugh Class B or C
• Pregnant women are excluded from this study.