A Study of the Efficacy of a New Treatment Option for Advanced Bile Duct Cancer of the Liver Using Immunotherapy and Targeted Radiation Therapy

Bile duct cancer (cholangiocarcinoma) is a rare but aggressive form of cancer. It originates in the bile ducts, which carry bile from the liver to the intestines, and can occur both within (intrahepatic) and outside (extrahepatic) the liver. This disease is often diagnosed at a late stage, when distant metastases have already spread to other organs. In most cases, a cure is no longer possible at this point, so the goal is to “keep the disease in check” for as long as possible. The standard treatment involves systemic chemotherapy (e.g., gemcitabine and cisplatin) in combination with immunotherapy (durvalumab). Another standard treatment is Y-90 SIRT therapy. This is a targeted radiation therapy in which radioactive particles are delivered directly into the liver via the bloodstream to irradiate the cancer locally while sparing the surrounding tissue as much as possible. New treatment options include not only the use of immunotherapy, such as checkpoint inhibitors, but also combinations of immunotherapies or targeted therapies.

The goal of this Phase 2 study is to determine whether checkpoint inhibitor therapy administered after radiation therapy can improve the response to treatment. The study will compare two drug therapies. As part of the study, patients are randomly assigned to two groups. First, all patients receive radiation therapy. Afterward, patients in Group 1 receive durvalumab as monotherapy. Patients in Group 2 will receive durvalumab in combination with tremelimumab, another immunotherapy. Both drugs are administered as intravenous infusions. The study is open-label, meaning that both the medical staff and the patients know which drugs are being administered. Immunotherapy will continue as long as it is effective and well tolerated. The primary endpoint of the study is the objective response rate (ORR) after 20 months—that is, the proportion of patients in whom a measurable reduction in tumor size is observed during treatment. Patients will be followed for up to 43 months to analyze long-term outcomes such as safety, survival, and disease progression.

Men and women with intrahepatic bile duct cancer who are at least 18 years old are eligible to participate in the study. The disease must be at an incurable stage, meaning it is either locally advanced within the liver and no longer operable, or has already metastasized outside the liver. However, there must be only a few metastases, and the disease must be stable overall. Patients may have previously received chemotherapy with capecitabine or gemcitabine + cisplatin. Patients must be eligible for radioimmunotherapy (SIRT).