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

Aichi Medical University

Status: Enrolling

Conditions: Extrahepatic Cholangiocarcinoma

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

Study type: Interventional

Funder types: Other

Identifiers

NCT07235007

BRAVE-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 120 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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120 participants in 2 patient groups

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

Experimental group

Description:

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.

Treatment:

Device: Endobiliary Radiofrequency Ablation (EB-RFA)

Device: Plastic Biliary Stent

Plastic Stenting + Durvalumab/Gemcitabine/Cisplatin

Active Comparator group

Description:

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.

Treatment:

Device: Plastic Biliary Stent