Prophylactic Endoscopic Variceal Ligation in Patients With High-risk Esophageal Varices Receiving Atezolizumab Plus Bevacizumab for Hepatocellular Carcinoma : A Phase II, Multicenter, Single-arm Trial (ESCOAT Trial)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 44
- 试验地点
- 2
- 主要终点
- The incidence of esophageal variceal bleeding at 6 months
研究概览
简要总结
The goal of this study is to evaluate whether prophylactic endoscopic variceal ligation (EVL) can prevent esophageal variceal bleeding in patients with hepatocellular carcinoma (HCC) receiving atezolizumab and bevacizumab (Atezo/Bev) therapy. The study will also assess the safety of prophylactic EVL in this population.
The main question it aims to answer is:
Does prophylactic EVL in high-risk varices reduce the incidence of variceal bleeding to a level similar to that of low-risk varices in HCC patients receiving Atezo/Bev?
Participants will:
- Undergo prophylactic EVL before starting Atezo/Bev therapy (within 2 weeks ± 1 week before the first dose).
- Start Atezo/Bev therapy 2 weeks (± 1 week) after EVL.
- Have follow-up endoscopies (EGD) one week after the 3rd, 5th, and 7th doses of Atezo/Bev.
If varices improve, no additional intervention is needed. If varices persist or worsen, on-demand EVL will be performed, and Atezo/Bev will continue.
This study will help determine if prophylactic EVL should be a standard strategy for managing high-risk varices in HCC patients undergoing Atezo/Bev therapy.
详细描述
- Backgrounds Patients with hepatocellular carcinoma (HCC) undergoing treatment with atezolizumab plus bevacizumab (Atezo/Bev) are at a high risk of variceal bleeding. When bleeding occurs, it may necessitate treatment delays or permanent discontinuation of Atezo/Bev, potentially requiring a switch to alternative anticancer therapies that may be less effective. Additionally, variceal bleeding can result in hepatic decompensation, deteriorated liver function, and reduced quality of life.
Prophylactic endoscopic variceal ligation (EVL) has been proposed as an approach to minimize the risk of variceal hemorrhage in patients with high-risk esophageal varices, as identified on screening endoscopy. By proactively treating high-risk varices before initiating Atezo/Bev, prophylactic EVL may optimize oncologic treatment continuity and overall patient outcomes. 2. Study aim
This Phase 2 study is designed to evaluate the efficacy and safety of prophylactic EVL in reducing variceal bleeding among HCC patients with high-risk esophageal varices undergoing Atezo/Bev therapy. In addition, this study aims to:
-
Assess the impact of prophylactic EVL on patient survival and quality of life.
-
Identify biomarkers associated with variceal bleeding risk and therapeutic response.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged 19 years or older and under 80 years.
- •Patients with liver function are classified as Child-Pugh Class A.
- •Barcelona Clinic Liver Cancer stage C patients with no prior systemic anticancer therapy for hepatocellular carcinoma.
- •Patients with an Eastern Cooperative Oncology Group performance score of 0-
- •Adequate Hematologic and Liver Function:
- •A. Hemoglobin: ≥ 9.0 g/dL B. Absolute Neutrophil Count : ≥ 1,000/mm³ C. Platelet Count: ≥ 70,000/μL D. Prothrombin Time: ≥ 70% (or Prothrombin Time INR ≤ 1.2)
- •Patients with upper gastrointestinal endoscopy performed within six months prior to the start of anticancer treatment.
- •No plans for breastfeeding, and if of childbearing potential, using contraception or no plans for spouse's pregnancy or practicing contraception.
- •Patients who have received an explanation of the treatment purpose and methods and have provided informed consent for the treatment.
排除标准
- •Participants who have previously received systemic anticancer therapy for advanced hepatocellular carcinoma.
- •Patients with intrahepatic tumor involvement of 50% or more.
- •Patients with tumor thrombus in the main portal vein or both first-order branches (Vp4).
- •Patients with a prior history of liver transplantation.
- •with uncontrolled malignant tumors other than HCC at the time of enrollment (participation is allowed if disease-free survival exceeds two years).
- •Patients with uncontrolled or serious underlying diseases requiring treatment.
- •Patients with a history of esophageal or gastric variceal bleeding.
- •Previous Variceal Treatments: Patients who have undergone any of the following treatments for variceal bleeding:
- •A. Endoscopic Variceal Obliteration (EVO) B. EVL C. Transjugular Intrahepatic Portosystemic Shunt (TIPS) D. Percutaneous Approach for Retrograde Transvenous Obliteration (PARTO) E. Surgical procedures
- •Patients who have used anticoagulants or antiplatelet agents within one week prior to the study.
- •Presence of grade 2 or higher isolated gastric varices or Red Color Signs confirmed by baseline endoscopy (EGD).
- •Patients who are pregnant.
- •Patients who are unable to understand or provide written informed consent.
- •Patients deemed unsuitable for clinical study participation based on the investigator's judgment.
结局指标
主要结局
The incidence of esophageal variceal bleeding at 6 months
时间窗: From the first Atezo/Bev treatment date until the date of first esophageal varix bleeding, Atezo/Bev treatment discontinuation, or last follow-up, whichever came first, assessed up to 6 months
The incidence of esophageal variceal bleeding at 6 months following treatment in patients with HCC receiving atezolizumab and bevacizumab as standard therapy.
次要结局
- Cumulative incidence of acute esophageal varix bleeding(from the date of the first Atezo/Bev treatment date until the date of first esophageal varix bleeding, the discontinuation of Atezo/Bev treatment or last follow-up, whichever came first, assessed up to 12 months)
- Cumulative incidence of liver-related complications (except for esophageal varix bleeding)(from the date of the first Atezo/Bev treatment date until the date of first liver-related complications (except for esophageal varix bleeding), the discontinuation of Atezo/Bev treatment or last follow-up, whichever came first, assessed up to 12 months)
- Cumulative incidence of non-variceal GI bleeding(from the date of the first Atezo/Bev treatment date until the date of first non-variceal GI bleeding, the discontinuation of Atezo/Bev treatment or last follow-up, whichever came first, assessed up to 12 months)
- Overall survival(from the date of the first Atezo/Bev treatment date until the date of death, the discontinuation of Atezo/Bev treatment or last follow-up, whichever came first, assessed up to 12 months)
- Incidence of EVL-related complications(from the date of the first Atezo/Bev treatment date until the date of first EVL-related complications, the discontinuation of Atezo/Bev treatment or last follow-up, whichever came first, assessed up to 12 months)
- Development of biomarker predicting occurrence of variceal bleeding and clinical outcome(through 24 weeks)
- Quality of Life Assessment Related to Treatment(Before the date of first EVL, first Atezo/Bev treatment date, and first/third EGD surveillance after first EVL)
研究者
Ju Hyun Shim
Professor
Asan Medical Center