Repeated Endobiliary Radiofrequency Ablation Plus Durvalumab, Gemcitabine, and Cisplatin for Unresectable Extrahepatic Cholangiocarcinoma

NCT ID: NCT07235007

Last Updated: 2026-01-13

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-11-20
• Study Completion Date: 2030-12-31

Brief Summary

This international, multicenter, open-label randomized controlled trial evaluates whether repeated endobiliary radiofrequency ablation (EB-RFA) improves overall survival in patients with unresectable extrahepatic cholangiocarcinoma undergoing first-line systemic therapy with durvalumab plus gemcitabine and cisplatin (GCD). Eligible patients will be randomized 1:1 to EB-RFA with plastic stent placement or standard plastic stenting alone. A scheduled second endoscopic session will be performed at 3 months in both groups (repeat EB-RFA only in the EB-RFA arm). The primary endpoint is overall survival. Secondary endpoints include time to recurrent biliary obstruction, progression-free survival, adverse events, and technical/clinical success.

Detailed Description

Extrahepatic cholangiocarcinoma (eCCA) frequently presents as unresectable disease with obstructive jaundice. Although gemcitabine, cisplatin plus durvalumab (GCD) is the global standard first-line regimen, median overall survival remains approximately one year. Endobiliary radiofrequency ablation (EB-RFA) is biologically plausible to enhance local tumor control by inducing coagulative necrosis at the biliary stricture. Retrospective studies, including a multicenter dataset from participating institutions, suggest a survival benefit of repeated EB-RFA, especially when combined with systemic therapy. However, prospective randomized evidence is lacking.

This trial (BRAVE) randomizes eligible patients to EB-RFA plus standardized endoscopic stenting or endoscopic stenting alone, followed by GCD. A planned second endoscopic session is performed at Month 3 (window 2-4 months). Additional EB-RFA sessions (≥2-month intervals) are permitted in the EB-RFA arm if imaging shows potentially ablatable lesions and clinical benefit is expected.

The study aims to determine whether repeated EB-RFA prolongs survival and improves biliary patency when integrated with modern systemic therapy.

Conditions

Extrahepatic Cholangiocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Endobiliary Radiofrequency Ablation + Plastic Stent + Durvalumab/Gemcitabine/Cisplatin

Participants undergo endobiliary radiofrequency ablation (EB-RFA) followed by placement of a plastic biliary stent during the index endoscopy. A scheduled second endoscopy at Month 3 (window 2-4 months) includes repeat EB-RFA and stent exchange. Additional EB-RFA sessions (≥2-month intervals) may be performed if imaging suggests a potentially ablatable residual biliary lesion. All participants receive systemic therapy with durvalumab, gemcitabine, and cisplatin according to institutional standards.

Group Type: EXPERIMENTAL

Endobiliary Radiofrequency Ablation (EB-RFA)

Intervention Type: DEVICE

Endobiliary RFA performed using the ELRA® catheter (STARmed) with VIVA combo® generator.

Recommended settings: 7-10 W, temperature control 80 °C, 120 seconds per application.

Applied along the full stricture length. Repeat procedure at Month 3 (window 2-4 months).

Additional sessions every ≥2 months permitted if imaging suggests ablatable residual lesion.

Plastic Biliary Stent

Intervention Type: DEVICE

Placement of 7Fr or 8.5Fr plastic biliary stent from hepatic side of the stenosis to the duodenum.

Bilateral preferred for hilar strictures; unilateral acceptable based on drainage.

Plastic Stenting + Durvalumab/Gemcitabine/Cisplatin

Participants receive standard endoscopic placement of a plastic biliary stent during the index endoscopy without EB-RFA. A scheduled elective stent exchange is performed at Month 3 (window 2-4 months). Additional elective stent exchanges every ≥2 months may be performed at the investigator's discretion. All participants receive systemic therapy with durvalumab, gemcitabine, and cisplatin according to institutional standards.

Group Type: ACTIVE_COMPARATOR

Plastic Biliary Stent

Intervention Type: DEVICE

Placement of 7Fr or 8.5Fr plastic biliary stent from hepatic side of the stenosis to the duodenum.

Bilateral preferred for hilar strictures; unilateral acceptable based on drainage.

Interventions

Endobiliary Radiofrequency Ablation (EB-RFA)

Endobiliary RFA performed using the ELRA® catheter (STARmed) with VIVA combo® generator.

Recommended settings: 7-10 W, temperature control 80 °C, 120 seconds per application.

Applied along the full stricture length. Repeat procedure at Month 3 (window 2-4 months).

Additional sessions every ≥2 months permitted if imaging suggests ablatable residual lesion.

Intervention Type: DEVICE

Plastic Biliary Stent

Placement of 7Fr or 8.5Fr plastic biliary stent from hepatic side of the stenosis to the duodenum.

Bilateral preferred for hilar strictures; unilateral acceptable based on drainage.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

Histologically or cytologically confirmed extrahepatic cholangiocarcinoma (eCCA).

Unresectable disease (unresectable due to tumor/patient factors, or patient refusal of surgery).

Biliary obstruction requiring drainage, demonstrated by abnormal cholestatic liver tests, elevated bilirubin, radiologic evidence, or existing biliary drainage.

Planned initiation of first-line systemic therapy with durvalumab + gemcitabine + cisplatin (GCD).

Age ≥18 years.

Able to provide written informed consent.

Exclusion Criteria

Prior radiotherapy or systemic therapy for the current eCCA.

Presence of a self-expanding metal stent that cannot be endoscopically removed.

Surgically altered anatomy except for Billroth-I; prior biliary reconstruction.

History of chronic cholangitis (e.g., primary sclerosing cholangitis, IgG4-related cholangitis).

Expected survival <3 months.

Inability to insert an oral endoscope or reach the papilla.

Contraindication to endobiliary RFA.

Pregnancy or possible pregnancy.

Any condition judged unsuitable by the investigator.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Aichi Medical University

OTHER

Sponsor Role: lead

Responsible Party

Tadahisa Inoue

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Tadahisa Inoue, Associate Professor

Role: PRINCIPAL_INVESTIGATOR

Department of Gastroenterology, Aichi Medical University

Jae Hee Cho, Professor

Role: PRINCIPAL_INVESTIGATOR

Department of Internal Medicine, Institute of Gastroenterology, Gangnam Severance Hospital, Yonsei University College of Medicine

Locations

Aichi Medical University

Aichi, , Japan

Site Status: RECRUITING

Nagoya City University Hospital

Aichi, , Japan

Site Status: RECRUITING

Nagoya City University Midori Municipal Hospital

Aichi, , Japan

Site Status: RECRUITING

Gifu University Hospital

Gifu, , Japan

Site Status: RECRUITING

Pusan National University Hospital

Busan, , South Korea

Site Status: RECRUITING

Gangnam Severance Hospital, Yonsei University College of Medicine

Seoul, , South Korea

Site Status: RECRUITING

Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine

Seoul, , South Korea

Site Status: RECRUITING

Severance Hospital, Yonsei University College of Medicine

Seoul, , South Korea

Site Status: RECRUITING

Countries

Japan; South Korea

Central Contacts

Tadahisa Inoue

Role: CONTACT

tinoue-tag@umin.ac.jp

+81561623311

Other Identifiers

BRAVE-001

Identifier Type: -

Identifier Source: org_study_id