The purpose of this research is to see if combining gemcitabine, cisplatin and Durvalumab chemotherapy treatments with a direct tumor therapy called Yittrium-90, will work better together to shrink the tumor and control cancer.
Adult males and females at least 18 years of age
Histologically and/or cytologically confirmed iCCA that is previously untreated or, if systemic therapy has been rendered for prior disease, has been administered at least 6 months before the development of recurrent or de novo new sites of disease.
Unresectable disease, as deemed by the Inova multidisciplinary tumor board (i.e. disease that cannot be safely resected with negative margins, leaving 2 adjacent segments of liver with intact portal venous and hepatic arterial inflow and intact biliary and hepatic venous outflow with the future liver remnant of sufficient volume to avoid postoperative liver insufficiency)
Measurable disease per RECIST 1.1 at least 2 cm in size
Female patients who are pregnant or breast-feeding
History of allogeneic organ transplantation.
Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
Patients with controlled type 1 diabetes on an insulin regimen are eligible for the study.
Single group
Induction Chemotherapy Triplet Therapy
DrugGemcitabine 1000 mg/m2, Cisplatin 25 mg/m2 infused on both day 1 and day 8 of a 21-day cycle. Durvalumab 1500 mg will be given on day 1 of each cycle.
Concurrent Y-90 treatment
RadiationPatients will undergo a Y-90 treatment planning consultation by the treating interventional radiologist during cycle 1. One or two cycles (depending on tumor size) of cisplatin, 25 mg/m2 and gemcitabine 300 mg/m2 given on day 1 and day 8 in combination with Yttrium-90 (Y-90) microspheres which will be given on day 3-7 or day 10-21 at the discretion of the interventional radiologist, separated in time by at least 2 days from a chemo infusion during that cycle
Consolidation Doublet Therapy:
DrugGemcitabine 1000 mg/m2 and Cisplatin 25 mg/m2 given on days 1 and 8 of a 21-day cycle with durvalumab 1500 mg given on day 1 of each cycle for 3-5 additional cycles. For the cycle directly after Y-90, gemcitabine will be kept at a dose of 300 mg/m2 to minimize risk of toxicity.
Assessing the objective response rate (ORR) at 6 months in patients with locally advanced, unresectable intrahepatic cholangiocarcinoma (iCCA)
Best response in terms of tumor shrinkage (by RECIST 1.1 criteria including complete + partial responses) obtained during protocol therapy.
Assessing Progression Free Survival (PFS)
time from treatment initiation to disease progression, death or last patient contact
Hepatic Progression-Free Survival (HPFS)
time from treatment initiation to hepatic disease progression, death or last patient contact
Overall Survival (OS)
Time from treatment initiation to death due to any cause or last patient contact
Disease Control Rate (DCR)
Complete Response + Partial Response + Stable Disease (by RECIST 1.1 and mRECIST criteria) obtained during protocol therapy.
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