Repeated endobiliary radiofrequency ablation with durvalumab, gemcitabine, and cisplatin for unresectable extrahepatic bile duct cancer
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 trial tests whether adding repeated endobiliary radiofrequency ablation to standard durvalumab plus gemcitabine and cisplatin helps people with unresectable extrahepatic bile duct cancer live longer.
Quick facts
| Phase | Not applicable |
|---|---|
| Study type | Interventional |
| Enrollment | 120 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Aichi Medical University Academic / other |
| Drugs / interventions | durvalumab |
| Locations | 8 sites (Aichi and 7 other locations) |
| Trial ID | NCT07235007 on ClinicalTrials.gov |
What this trial studies
BRAVE is an open-label, randomized multicenter trial that assigns patients 1:1 to repeated endobiliary radiofrequency ablation (EB-RFA) with plastic stent placement or to plastic stenting alone, with all participants receiving first-line durvalumab plus gemcitabine and cisplatin (GCD). A planned second endoscopic session at month 3 (window 2–4 months) allows repeat EB-RFA in the EB-RFA arm and standardized stent management in both arms, and additional EB-RFA sessions (≥2-month intervals) are permitted if imaging suggests an ablatable lesion. The primary endpoint is overall survival, and secondary endpoints include time to recurrent biliary obstruction, progression-free survival, adverse events, and technical/clinical success. The trial builds on retrospective multicenter data suggesting a survival benefit with repeated EB-RFA but will provide prospective randomized evidence integrated with modern immunochemotherapy.
Who should consider this trial
Good fit: Adults with histologically or cytologically confirmed unresectable extrahepatic cholangiocarcinoma who require biliary drainage and are planning first-line treatment with durvalumab plus gemcitabine and cisplatin are ideal candidates.
Not a fit: Patients with prior radiotherapy or systemic therapy for the current cancer, non-removable self-expanding metal stents, surgically altered anatomy preventing endoscopic access, active chronic cholangitis, contraindications to endobiliary RFA, or expected survival under three months may not benefit or be ineligible.
Why it matters
Potential benefit: If successful, this approach could extend overall survival and improve the durability of biliary drainage for patients with unresectable extrahepatic cholangiocarcinoma.
How similar studies have performed: Retrospective and multicenter datasets, including data from participating centers, suggest a survival benefit with repeated EB-RFA combined with systemic therapy, but prospective randomized evidence is currently lacking.
Eligibility criteria
Show full inclusion / exclusion 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.
Where this trial is running
Aichi and 7 other locations
- 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)
Study contacts
- Principal investigator: Tadahisa Inoue, Associate Professor — Department of Gastroenterology, Aichi Medical University
- Study coordinator: Tadahisa Inoue
- Email: tinoue-tag@umin.ac.jp
- Phone: +81561623311
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.