An interventional study of Endobiliary Radiofrequency Ablation (EB-RFA) and Plastic Biliary Stent in Extrahepatic Cholangiocarcinoma, sponsored by Aichi Medical University. Recruiting at 8 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-01-13.
Sponsored by Aichi Medical University · Not applicable, Interventional, and Treatment
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.
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.
914 studies on the registry are indexed under Cholangiocarcinoma; 286 are open to participants now.
This study's planned enrollment of 120 is above the median of 50 across 687 interventional studies indexed under Cholangiocarcinoma.
Browse Cholangiocarcinoma studies →Aichi Medical University is the lead sponsor of 3 studies on the registry; 2 are open to participants now.
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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.
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
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
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.
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.
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.
Time frame: From randomization until death from any cause (up to 36 months after last enrollment)
Time to Recurrent Biliary Obstruction (TRBO)
TRBO is defined as the time from stent placement to recurrent biliary obstruction (RBO).
Time frame: From stent placement to RBO or censoring (up to 36 months)
Progression-Free Survival (PFS)
Progression-free survival is defined per RECIST v1.1 based on imaging performed every 2-4 months.
Time frame: From randomization to radiologic progression or death (up to 36 months)
Non-RBO Survival
Time alive without recurrent biliary obstruction.
Time frame: Up to 36 months
Survival Free From Late Biliary-Procedure-Related Adverse Events
Late adverse events are defined as events occurring ≥15 days after the procedure (Tokyo Criteria 2024).
Time frame: Up to 36 months
Incidence and Etiology of Recurrent Biliary Obstruction (RBO)
Number and types of RBO events and their causes (sludge, tumor ingrowth/overgrowth, migration, dysfunction).
Time frame: Up to 36 months
Early Adverse Events (≤14 days)
Procedure-related adverse events within 14 days, graded by Tokyo Criteria 2024.
Time frame: 14 days
Late Adverse Events (≥15 days)
Procedure-related adverse events occurring ≥15 days post-procedure.
Time frame: Up to 36 months
Technical Success
Successful completion of the intended procedure: EB-RFA + plastic stent placement in the experimental arm Plastic stent placement in the comparator arm
Time frame: At index procedure
Clinical Success
Defined as: Hyperbilirubinemia: total bilirubin reduction ≥50% or ≤1.5 mg/dL within 14 days Others: normalization of ≥2 abnormal cholestatic/hepatocellular enzymes If baseline values are normal after prior drainage, absence of re-worsening beyond abnormal thresholds.
Time frame: Within 14 days after stent placement
Number of RBO Events
Count of recurrent biliary obstruction events per participant.
Time frame: Up to 36 months
Number of Endoscopic Reinterventions
Total number of endoscopic procedures including therapeutic interventions required during follow-up.
Time frame: Up to 36 months
Plan to share: No
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