Durvalumab + Intraductal Radiofrequency Ablation (ID-RFA) in Extra- and Intrahepatic Cholangiocarcinoma

The present clinical trial is a prospective, investigator-initiated, single-arm, open-label, multicenter phase II trial. Patients with unresectable perihilar and/or ductal or intrahepatic CCA with indication for bile duct stenting and palliative systemic therapy as determined by the local multidisciplinary team (MDT), who already resolved cholestasis due to RFA + Stent will be enrolled. We hypothesize that in patients with extra- and intrahepatic cholangiocarcinoma, the use of a combination radiofrequency ablation followed by systemic treatment with chemotherapy plus durvalumab might further increase the anti-tumor activity.

Inclusion Criteria: 1. Patient\* has given written informed consent. 2. Patient is ≥ 18 years of age at time of signing the written informed consent. 3. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. 4. Patient has been diagnosed with histologically or cytologically confirmed 1. histologically or cytologically confirmed cholangiocarcinoma as adenocarcinoma of pancreatobiliary type 2. unresectable perihilar and/or ductal extrahepatic cholangiocarcinoma or intrahepatic CCA with perihilar stricture according to Bismuth-Corlette classification with indication for bile duct stenting and palliative systemic therapy as determined by the local multidisciplinary team (MDT) and already resolved cholestasis due to RFA + stent 5. Patient tolerated RFA prior to inclusion and is eligible for repeat RFA during the study (does not have any contraindications) as determined by investigator. 6. Patient is eligible for palliative systemic therapy based on clinical and laboratory parameters (except hyperbilirubinemia) as determined by the local MDT 7. Patient has a ECOG ≤ 1. 8. Patient has life expectancy of ≥ 12 weeks 9. Patient has body weight \> 30 kg 10. Adequate blood count, liver-enzymes, and renal function: 1. ANC \> 1,500 cells/μL without the use of hematopoietic growth factors 2. Platelet count ≥ 100 x 109/L (\>100,000 per mm3) 3. Hemoglobin ≥ 9 g/dL 4. Serum total bilirubin ≤ 3x upper normal limit (ULN) (biliary drainage is allowed for biliary obstruction; elevated bilirubin should be caused by obstruction not impaired liver function as assessed by albumin and INR values) 5. Albumin levels ≥ 2.8 g/dL 6. Patients not receiving therapeutic anticoagulation must have an INR\< 2.0 ULN and PTT \< 1.5 ULN within 7 days prior to randomization. The use of full dose anticoagulants is allowed as long as the INR or PTT is within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose for anticoagulants for at least three weeks at the time of inclusion 7. AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional ULN unless liver metastases are present, in which case it must be ≤ 5x ULN 8. Serum Creatinine ≤ 1.5 x ULN and a calculated creatinine clearance rate ≥ 60 mL /min 11. Female patients defined as women of childbearing potential (WOCBP) or male patients with WOCBP partners must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \