Phase 1 Trial of Safety and Preliminary Efficacy of Segmental Ablative Radioembolization in Combination With Tremelimumab Plus Durvalumab (MEDI4736) in Patients With Unresectable, or Oligo-Metastatic Cholangiocarcinoma Who Are Not Candidates for Curative Therapy (RAIDEN Trial)
This phase I trial tests the safety and side effects of yttrium-90 (Y90) radioembolization combined with immunotherapy drugs tremelimumab and durvalumab in treating patients with intrahepatic cholangiocarcinoma (cancer of the bile ducts in the liver) that has spread to nearby tissue or lymph nodes (locally advanced) and cannot be removed by surgery (unresectable) who are not candidates for curative therapy or that has spread from where it first started (primary side) to multiple other places in the body (oligo-metastatic). Cholangiocarcinoma is a rare but aggressive cancer with limited curative options outside of surgery. Immunotherapy has shown modest benefit in hepatobiliary (liver, bile ducts, and gallbladder) cancers including cholangiocarcinoma. Radioembolization is a type of radiation therapy used to treat liver cancer that is advanced or has come back where tiny beads that hold the radioactive substance (radioisotope) yttrium Y90 are injected into or near the hepatic artery (the main blood vessel that carries blood to the liver). The beads collect in the tumor and the Y90 gives off radiation. This destroys the blood vessels that the tumor needs to grow and kills the tumor cells. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving Y90 radioembolization in combination with tremelimumab and durvalumab immunotherapy may be safe and beneficial in treating patients with locally advanced, unresectable or oligo-metastatic intrahepatic cholangiocarcinoma who are not candidates for curative therapy.
• Age \>= 18 years with body weight \> 30 kg
• Histologically or cytologically confirmed, locally advanced intrahepatic cholangiocarcinoma that is not amenable to resection, transplantation, or thermal ablation. Oligometastatic intrahepatic cholangiocarcinoma is also eligible. Specifically, such patients must have EITHER =\< 3 malignant extrahepatic lymph nodes (short axis diameter \>= 3cm) OR metastatic lesions in one organ other than liver (if only single lesion is present diameter MUST be \< 3cm, if up to 3 lesions in one organ each lesion MUST be =\< 1cm)
• Measurable disease
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• Hemoglobin \>= 9.0 g/dL (=\< 14 days prior to registration)
• Absolute neutrophil count (ANC) \>= 1000/mm\^3 (=\< 14 days prior to registration)
• Platelet count \>= 75,000/mm\^3 (=\< 14 days prior to registration)
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) (patients with known Gilbert disease who have serum bilirubin level 3 x ULN may be enrolled) (=\< 14 days prior to registration)
• Alanine aminotransferase (ALT) and aspartate transaminase (AST) =\< 5 x ULN (=\< 14 days prior to registration)
• Calculated creatinine clearance \>= 40 ml/min using the Cockcroft- Gault formula or measured creatinine clearance \> 40 ml/min (=\< 14 days prior to registration)
• International normalized ratio (INR) =\< 1.6. Note: INR prolongation due
‣ Anticoagulation (INR \>= 2.0 but =\< 3.0)) for prophylaxis in patients without liver cirrhosis could be exception
• Adequate hepatic function Child Pugh A and albumin-bilirubin (ALBI) 1 or 2
• Patients with concurrent hepatitis B (HBV) or hepatitis C virus (HCV) infection should meet the following criteria:
‣ Patient with HBV or should be monitored for viral levels during study participation
⁃ Patient with detectable hepatitis B surface antigen (HBsAg) or detectable HBV DNA should have HBV DNA \< 100 IU/ml and should be managed per local guidelines
⁃ Controlled hepatitis B subjects will be allowed if they have started treatment prior to or by the time point of enrollment into the study and treatment is continued during study participation and for \>= 6 months after end of study treatment
⁃ Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
• Negative urine pregnancy test done prior =\< 7 days registration, for persons of childbearing potential only
‣ NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required