Endoscopy and Radiology-guided Ablation for Inoperable Cholangiocarcinoma (COMBO-RFA)

A Combined Endoscopy and Radiology-guided Radiofrequency Ablation Therapy Protocol for Inoperable Perihilar Cholangiocarcinoma

This prospective clinical trial aims to assess the feasibility, efficacy, and safety of a personalized radiofrequency ablation protocol coupled with complete biliary drainage for patients presenting with inoperable perihilar cholangiocarcinoma.

This clinical trial proposes a personalized treatment approach to inoperable perihilar cholangiocarcinoma consisting of endoluminal ablative therapy via radiofrequency ablation followed by endoscopic biliary drainage. The main study objectives are: To assess the technical feasibility of implementing the proposed therapeutic protocol involving a combined endoscopic-radiologic approach to drainage and ablation To evaluate the efficacy of radiofrequency ablation in local disease control To evaluate whether complete drainage and radiofrequency ablation have a cumulative benefit in patients with inoperable perihilar cholangiocarcinoma To evaluate the safety of our proposed therapeutic protocol combining interventional endoscopy with radiology

Patients randomized to this arm will undergo same-session endoluminal radiofrequency ablation followed by biliary stenting

Endoluminal Radiofrequency ablation (RFA) of the entire stricture length will be performed using the Habib probe. A current of 7W will be delivered for 90s intervals at a time. If multiple ablation sessions are needed in order to ablate the entire stricture lenght, there will be an overlap of ablated areas in order to ensure proper stricture treatment. Dilation of the stricture prior to RFA delivery will be performed if required. After RFA treatment, biliary drainage of all hepatic territories will be ensured.

Endoscopic biliary stenting will be performed via ERCP using multiple plastic stents, in order to ensure propper drainage of all accessed hepatic territories.

Ability to correctly apply radiofrequency ablation and place stents in all the biliary ducts accessed on ERCP

To evaluate the efficacy of radiofrequency ablation in local disease control by assessing tumor response according to RECIST criteria at 6 months follow-up

To evaluate the safety profile of the procedure by assessing the rate of procedure-related adverse events according to the ASGE lexicon (cholangitis, bleeding, perforation, pancreatitis) after endoscopic treatment

To evaluate the expression of programmed death (PD)-1 / PD- ligand 1 markers on biopsy samples of tumor tissue obtained at the index and follow-up ERCP procedure

Inclusion Criteria: perihilar cholangiocarcinoma locally advanced disease (unresectable) M1 (limted to 1 site) Exclusion Criteria: refusal to sogn the ICF poor performance status (ECOG >2) surgically altered anatomy (i.e Bilroth II or Roux-en-Y interventions) significant comorbidities ASA score >3 life expectancy <3 months