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

NCT07235007 | Recruiting DMC

• 1 other identifier: BRAVE-001
• Study Type: interventional
• Target: 120
• Locations: 2 countries
• Sites: 8

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.

Conditions

Extrahepatic Cholangiocarcinoma

Keywords

Extrahepatic Cholangiocarcinoma; Cholangiocarcinoma; Biliary Tract Cancer; Bile Duct Stricture; Endobiliary Radiofrequency Ablation (EB-RFA); Radiofrequency Ablation; Endoscopic Retrograde Cholangiopancreatography (ERCP); Gemcitabine; Cisplatin; Durvalumab; Recurrent Biliary Obstruction (RBO)

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  Overall survival is defined as the time from randomization to death from any cause. Participants still alive at the last confirmed contact will be censored at that date.

  From randomization until death from any cause (up to 36 months after last enrollment)

Secondary Outcomes (11)

• Time to Recurrent Biliary Obstruction (TRBO)

  From stent placement to RBO or censoring (up to 36 months)

• Progression-Free Survival (PFS)

  From randomization to radiologic progression or death (up to 36 months)

• Non-RBO Survival

  Up to 36 months

• Survival Free From Late Biliary-Procedure-Related Adverse Events

  Up to 36 months

• Incidence and Etiology of Recurrent Biliary Obstruction (RBO)

  Up to 36 months

Study Arms (2)

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

EXPERIMENTAL

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.

Device: Endobiliary Radiofrequency Ablation (EB-RFA); Device: Plastic Biliary Stent

Plastic Stenting + Durvalumab/Gemcitabine/Cisplatin

ACTIVE COMPARATOR

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.

Device: Plastic Biliary Stent

Interventions

Endobiliary Radiofrequency Ablation (EB-RFA) 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.

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

Plastic Biliary Stent 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.

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Aichi Medical University: lead

Study Sites (8)

Aichi Medical University

Aichi, Japan

RECRUITING

Nagoya City University Hospital

Aichi, Japan

RECRUITING

Nagoya City University Midori Municipal Hospital

Aichi, Japan

RECRUITING

Gifu University Hospital

Gifu, Japan

RECRUITING

Pusan National University Hospital

Busan, South Korea

RECRUITING

Gangnam Severance Hospital, Yonsei University College of Medicine

Seoul, South Korea

RECRUITING

Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine

Seoul, South Korea

RECRUITING

Severance Hospital, Yonsei University College of Medicine

Seoul, South Korea

RECRUITING

MeSH Terms

Conditions

Cholangiocarcinoma; Biliary Tract Neoplasms

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Biliary Tract Diseases; Digestive System Diseases

Study Officials

• Tadahisa Inoue, Associate Professor

  Department of Gastroenterology, Aichi Medical University

  PRINCIPAL INVESTIGATOR

• Jae Hee Cho, Professor

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tadahisa Inoue

CONTACT

+81561623311; tinoue-tag@umin.ac.jp

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: November 16, 2025
• First Posted: November 19, 2025
• Study Start: November 20, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2030
• Last Updated: January 13, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

KR (4); JP (4)