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.

Study Overview

• Status: Active, not recruiting
• Conditions: Perihilar Cholangiocarcinoma
• Intervention / Treatment: Procedure: Endoscopic biliary stenting; Procedure: Endoluminal radiofrequency ablation

Detailed Description

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.

Patients presenting with jaundice / biliary obstruction caused by inoperable perihilar cholangiocarcinoma as assessed during multidisciplinary case discussion will be invited to enroll in this trial.

Patients will be randomized in a 1:1 fashion to receive biliary plastic stenting (control arm) or biliary plastic stenting + radiofrequency ablation via endoscopic approach. In cases where ERCP fails to achieve adequate biliary drainage, stenting and/or drainage will be attempted via percutaneous approach.

Additional systemic chemotherapy will be offered to all eligible patients according to the local standard of care.

Patients will be followed up with a clinical visit at 2 weeks and stent exchange (+ additional RFA treatment in the control arm) will be offered at 8-12 weeks interval until disease progression, clinical deterioration precluding ERCP or death.

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

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Theodor Voiosu; Phone Number: +40726732764; Email: theodor.voiosu@gmail.com
• Study Contact Backup: Name: Claudia Diaconu; Phone Number: +40763107021; Email: puscasu_ic@yahoo.com

Study Locations

• Romania
  • Bucharest, Romania, 020125
    • Gastroenterology Department, Colentina Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Endoscopic Drainage Arm; Patients randomized to this arm will undergo biliary stenting only	Procedure: Endoscopic biliary stenting; Endoscopic biliary stenting will be performed via ERCP using multiple plastic stents, in order to ensure propper drainage of all accessed hepatic territories.
Experimental: COMBO-RFA Arm; Patients randomized to this arm will undergo same-session endoluminal radiofrequency ablation followed by biliary stenting	Procedure: Endoscopic biliary stenting; Endoscopic biliary stenting will be performed via ERCP using multiple plastic stents, in order to ensure propper drainage of all accessed hepatic territories.; Procedure: Endoluminal radiofrequency ablation; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Technical success of ERCP procedure	Ability to correctly apply radiofrequency ablation and place stents in all the biliary ducts accessed on ERCP	2 months
Tumor response	To evaluate the efficacy of radiofrequency ablation in local disease control by assessing tumor response according to RECIST criteria at 6 months follow-up	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of procedure-related adverse events	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	12 months
Overall survival	To assess patient survival rates at 12 months follow-up	12 months
Tumor microenvironment alterations	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	2 months

Collaborators and Investigators

• Sponsor: Clinical Hospital Colentina
• Collaborators: Carol Davila University of Medicine and Pharmacy; Universitatea din Bucuresti

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2022
• Primary Completion (Estimated): October 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: September 20, 2022
• First Submitted That Met QC Criteria: September 29, 2022
• First Posted (Actual): October 3, 2022

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: ERCP; Radiofrequency ablation; perihilar cholangiocarcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Cholangiocarcinoma; Klatskin Tumor
• Other Study ID Numbers: COMBO-RFA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No