Extrahepatic CholangiocarcinomaBRAVENCT07235007
Repeated Endobiliary Radiofrequency Ablation Plus Durvalumab, Gemcitabine, and Cisplatin for Unresectable Extrahepatic Cholangiocarcinoma
A study testing Endobiliary Radiofrequency Ablation (EB-RFA) and Plastic Biliary Stent in people with Extrahepatic Cholangiocarcinoma, run by Aichi Medical University at 8 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Extrahepatic Cholangiocarcinoma
- What is being tested?
- Endobiliary Radiofrequency Ablation (EB-RFA) and Plastic Biliary Stent
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 8 sitesin 2 countries
- Study dates
- 20 Nov 2025to 31 Dec 2030
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- Contraindication to endobiliary RFA.
- Pregnancy or possible pregnancy.
- Any condition judged unsuitable by the investigator.
Trial locations and contacts
8 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
8 sites in 2 countries
Japan4 sites, 4 recruiting
- Recruiting
Aichi Medical University
Aichi
- Recruiting
Nagoya City University Hospital
Aichi
- Recruiting
Nagoya City University Midori Municipal Hospital
Aichi
- Recruiting
Gifu University Hospital
Gifu
South Korea4 sites, 4 recruiting
- Recruiting
Pusan National University Hospital
Busan
- Recruiting
Gangnam Severance Hospital, Yonsei University College of Medicine
Seoul
- Recruiting
Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine
Seoul
- Recruiting
Severance Hospital, Yonsei University College of Medicine
Seoul
About this study
Official title: Survival Impact of Repeated Endobiliary Radiofrequency Ablation in Patients Undergoing Durvalumab Plus Gemcitabine and Cisplatin for Extrahepatic Cholangiocarcinoma: An International Multicenter Randomized Controlled Trial (BRAVE Trial)
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.
Read the 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
- Being tested
- Endobiliary Radiofrequency Ablation (EB-RFA), Plastic Biliary Stent
- 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)
- Medical subject headings
- Cholangiocarcinoma, Biliary Tract Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
Plastic Biliary StentDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Device: Plastic Biliary Stent |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From randomization until death from any cause (up to 36 months after last enrollment)
Secondary outcomes (11)
Time to Recurrent Biliary Obstruction (TRBO)
TRBO is defined as the time from stent placement to recurrent biliary obstruction (RBO).
Measured: 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.
Measured: From randomization to radiologic progression or death (up to 36 months)
Non-RBO Survival
Time alive without recurrent biliary obstruction.
Measured: 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).
Measured: 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).
Measured: Up to 36 months
Early Adverse Events (≤14 days)
Procedure-related adverse events within 14 days, graded by Tokyo Criteria 2024.
Measured: 14 days
Late Adverse Events (≥15 days)
Procedure-related adverse events occurring ≥15 days post-procedure.
Measured: 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
Measured: 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.
Measured: Within 14 days after stent placement
Number of RBO Events
Count of recurrent biliary obstruction events per participant.
Measured: Up to 36 months
Number of Endoscopic Reinterventions
Total number of endoscopic procedures including therapeutic interventions required during follow-up.
Measured: Up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2025
- Study start20 Nov 2025
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Extrahepatic CholangiocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Aichi Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tadahisa Inoue, Aichi Medical University
- Investigators
- Tadahisa Inoue, Associate Professor, Principal investigator, Department of Gastroenterology, Aichi Medical UniversityJae Hee Cho, Professor, Principal investigator, Department of Internal Medicine, Institute of Gastroenterology, Gangnam Severance Hospital, Yonsei University College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07235007
- Sponsor's protocol ID
- BRAVE-001
- Acronym
- BRAVE
- Status last verified
- Nov 2025
- First submitted
- 16 Nov 2025
- Last updated
- 13 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No