This phase II trial tests the safety and effectiveness of preoperative immunotherapy with durvalumab and chemotherapy with cisplatin and gemcitabine with or without futibatinib targeted therapy in treating patients with intrahepatic cholangiocarcinoma that can be removed by surgery (resectable). Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. Gemcitabine is a chemotherapy drug that blocks the cells from making deoxyribonucleic acid (DNA) and may kill cancer cells. Futibatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving immunotherapy with durvalumab and chemotherapy with cisplatin and gemcitabine and/or targeted therapy with futibatinib before surgery may make the tumor smaller for resection and may help prevent the cancer from coming back. Patients whose molecular profiling test result show a genetic change called FGFR2 fusion, rearrangement, or activating mutation, receive immunotherapy, chemotherapy and targeted therapy while patients without a FGFR2 fusion, rearrangement, or activating mutation just receive immunotherapy and chemotherapy. Giving targeted therapy based on molecular profile test results prior to attempted resection for patients with intrahepatic cholangiocarcinoma that has a risk for either not being able to be removed or for coming back after it has been removed may help improve treatment outcomes in patients with resectable intrahepatic cholangiocarcinoma.
Patients must have a confirmed biopsy proven diagnosis of resectable intrahepatic cholangiocarcinoma (IHCC) confined to the liver, bile duct, and /or regional lymph nodes confirmed by high-quality cross-sectional imaging by CT or MRI of the chest and MRI of the abdomen, and pelvis performed within 42 days (6 weeks) prior to enrollment. (MRI protocol: With and without gadolineum with T1 and T2 weighted sequences)
Note: Distant extrahepatic disease is not allowed
Note: When using CTs in addition to MRI, a high resolution triple phase thin-cut, CT with intravenous +/- oral contrast is the preferred imaging technique for assessing radiographic tumor response
Patients must have measurable disease per RECIST 1.1
Patients with peripheral neuropathy of grade 2 or greater by Common Terminology Criteria for Adverse Events (CTCAE) 5.0. In CTCAE version 5.0 grade 2 sensory neuropathy is defined as "moderate symptoms; limiting instrumental activities of daily living (ADLs)
Patients who are receiving any other investigational agents
Patients who have current evidence of corneal or retinal disorder/keratopathy including, but not limited to, bullous/band keratopathy, inflammation or ulceration, keratoconjunctivitis, confirmed by ophthalmic examination
Note: Patients with asymptomatic ophthalmic conditions assessed by the investigator to pose minimal risk for study participation may be enrolled in the study
Northwestern University
Lead sponsor
National Cancer Institute (NCI)
Collaborator