Overview
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.
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.
Eligibility
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.