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)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 8
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Endobiliary Radiofrequency Ablation + Plastic Stent + Durvalumab/Gemcitabine/Cisplatin
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.
干预措施: Endobiliary Radiofrequency Ablation (EB-RFA) (Device)
Endobiliary Radiofrequency Ablation + Plastic Stent + Durvalumab/Gemcitabine/Cisplatin
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.
干预措施: Plastic Biliary Stent (Device)
Plastic Stenting + Durvalumab/Gemcitabine/Cisplatin
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.
干预措施: Plastic Biliary Stent (Device)
结局指标
主要结局
Overall Survival (OS)
时间窗: From randomization until death from any cause (up to 36 months after last enrollment)
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.
次要结局
- Progression-Free Survival (PFS)(From randomization to radiologic progression or death (up to 36 months))
- Time to Recurrent Biliary Obstruction (TRBO)(From stent placement to RBO or censoring (up to 36 months))
- Non-RBO Survival(Up to 36 months)
- Survival Free From Late Biliary-Procedure-Related Adverse Events(Up to 36 months)
- Incidence and Etiology of Recurrent Biliary Obstruction (RBO)(Up to 36 months)
- Early Adverse Events (≤14 days)(14 days)
- Late Adverse Events (≥15 days)(Up to 36 months)
- Technical Success(At index procedure)
- Clinical Success(Within 14 days after stent placement)
- Number of RBO Events(Up to 36 months)
- Number of Endoscopic Reinterventions(Up to 36 months)
研究者
Tadahisa Inoue
Associate Professor
Aichi Medical University