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
Parallel
Biospecimen Collection
Procedure/SurgeryUndergo blood and previously collected tissue sample collection
Cisplatin
DrugGiven IV
Computed Tomography
Procedure/SurgeryUndergo CT
Durvalumab
Biological/VaccineGiven IV
Futibatinib
DrugGiven PO
Gemcitabine
DrugGiven IV
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Completion of all preoperative testing and therapy
Treatment completion is defined as completion of next generation sequencing testing and all preoperative and operative therapy. Will record the completion of all therapy rate, along with the exact 95% binomial confidence interval.
Incidence of Treatment-Emergent Adverse Events during all preoperative testing and therapy
Unacceptable toxicity is defined as any grade 3 or higher toxicities by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 that result in a treatment delay of \> 28 days.
Radiological response rate
Will be assessed by according to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) and defined as the percentage of patients who will have complete response, partial response or stable disease after the neoadjuvant therapy.
Pathologic response rate (PRR)
Will be defined as the degree of treatment effect to preoperative therapy. Pathologic complete response (pCR) will be defined as no viable tumor cells (0% viable tumor, 100% necrosis or fibrosis). Absent response will be defined as 100% viable tumor cells with no evidence of tumor regression. Partial response will be defined as degree of necrosis or fibrosis in the tumor bed, rounded to the nearest 10% interval. This is an endpoint to assess the pathologic response to futibatinib in those with FGFR2 fusions / rearrangements / activating mutations compared to cytotoxic chemotherapy in those without FGFR2 fusions/alterations. Pathological response will be measured by a three-tier response rate using pathologic (p) complete response = 0% tumor cells, no response = no histologic evidence of tumor regression and partial response = % necrosis and evident tumor regression. PRR will be calculated by Northwestern's pathologists with subspecialty training in gastrointestinal pathology.
Response by measuring circulating tumor deoxyribonucleic acid in the blood samples of patients with resectable intrahepatic cholangiocarcinoma
R0 resection rate
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Northwestern University
Lead sponsor
National Cancer Institute (NCI)
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
