Prophylactic Endoscopic Variceal Ligation in Patients With High-risk Esophageal Varices Receiving Atezo/Bev for HCC (ESCOAT)

July 21, 2025 updated by: Ju Hyun Shim, Asan Medical Center

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)

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:

  1. Undergo prophylactic EVL before starting Atezo/Bev therapy (within 2 weeks ± 1 week before the first dose).
  2. Start Atezo/Bev therapy 2 weeks (± 1 week) after EVL.
  3. 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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

  1. 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.

3. Study Design

  1. Prophylactic EVL Procedure Prophylactic EVL will be performed within two weeks (± 1 week) before the initiation of Atezo/Bev therapy. The procedure will be conducted by board-certified gastroenterological endoscopists with expertise in therapeutic endoscopy.

    - EVL technique: Suctioning of esophageal varices until the red-out phenomenon occurs. Placement of a rubber band at the variceal base to induce thrombus formation, leading to subsequent necrosis and sloughing. The procedure begins at the distal esophageal varices and progresses spirally upward. Priority treatment will be given to varices with active bleeding or endoscopic signs of recent hemorrhage.

  2. Follow-Up Endoscopy and Additional EVL Criteria Follow-up esophagogastroduodenoscopy (EGD) will be conducted one week after the 3rd dose of Atezo/Bev to assess variceal status.

    If any of the following criteria are met, additional EVL will not be performed, and Atezo/Bev therapy will continue two weeks later:

    • Varices have regressed to F1 or less
    • Red color signs have disappeared If these criteria are not met, an on-demand EVL session will be performed.
  3. Further On-Demand EVL Strategy Additional on-demand EVL sessions will be considered after the 5th and 7th doses of Atezo/Bev, with EGD follow-up before each session.

The maximum number of EVL sessions will be limited to three during the study period.

Study Type

Interventional

Enrollment (Estimated)

44

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Korea, Republic of
    • Song-pa
      • Seoul, Song-pa, Korea, Republic of, 05505
        • Recruiting
        • Liver cancer center, Asan Medical Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • Ju Hyun Shim, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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 0-1.
  • 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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: EVL group
This group is single arm which undergo prophylactic endoscopic variceal ligation for high-risk esophageal varices
Procedure: Endoscopic variceal ligation (EVL)
  1. EVL for high-risk varices will be performed by experienced endoscopists, certified in gastroenterological endoscopy, within two weeks prior to the initiation of the Atezo/Bev.

  2. A follow-up EGD will be conducted one week after the Atezo/Bev #3. If any of the following criteria are met, additional EVL will not be performed, and anticancer treatment will proceed two weeks later. Otherwise, an additional on-demand EVL session will be conducted:

    • The esophageal varices have improved to F1 or less.
    • The red color sign has disappeared.
  3. On-demand EVL will be considered after 5th, and 7th consecutive doses of Atezo/Bev, with EGD follow-up performed to assess eligibility. The maximum number of EVL sessions is limited to three sessions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The incidence of esophageal variceal bleeding at 6 months
Time Frame: 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.
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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cumulative incidence of acute esophageal varix bleeding
Time Frame: 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 acute esophageal varix bleeding after initiation of Atezo/Bev: acute esophageal varix bleeding is defined as:

i) Current oozing or spurting type bleeding on the esophageal varix ii) Stigmata suggesting recent bleeding (pin-point ulceration on the varix, adherent clot, or white protrusion in the setting of hematemesis but no other cause of UGI bleeding) iii) Post-EVL ulcer bleeding is also considered 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 non-variceal GI bleeding
Time Frame: 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
non-variceal GI bleeding is defined as new-onset hematemesis, melena or both combined with overall hemorrhage from the upper GI tract except for esophageal varix 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
Time Frame: 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
Overall survival will be evaluated
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
Cumulative incidence of liver-related complications (except for esophageal varix bleeding)
Time Frame: 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
liver-related complication is defined as ascites, spontaneous bacterial peritonitis, and hepatic encephalopathy
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
Incidence of EVL-related complications
Time Frame: 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
EVL-related complications will be evaluate after initiation of first EVL
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
Quality of Life Assessment Related to Treatment
Time Frame: Before the date of first EVL, first Atezo/Bev treatment date, and first/third EGD surveillance after first EVL

Patient-reported outcomes will be assessed using validated QoL instruments that are widely used in clinical trials for HCC and systemic therapy:

  1. EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30) Scoring: Each domain is scored on a 0-100 scale, with higher scores in functional scales indicating better QoL, while higher scores in symptom scales indicate greater symptom burden.
  2. EORTC QLQ-HCC18 (HCC-Specific Module) Scoring: Symptoms are rated on a scale of 1 to 4 (1 = not at all, 4 = very much). Higher scores indicate worse symptoms.
Before the date of first EVL, first Atezo/Bev treatment date, and first/third EGD surveillance after first EVL
Development of biomarker predicting occurrence of variceal bleeding and clinical outcome
Time Frame: through 24 weeks
A total of 20 mL of peripheral blood will be collected. If these samples are not collected during the scheduled visits, they may be obtained at any time during the clinical trial. Additional samples may also be collected depending on the patient's clinical condition.
through 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Asan Medical Center

Collaborators

National Cancer Center, Korea
Samsung Medical Center
Seoul National University Hospital
Seoul National University Bundang Hospital
Hanyang University

Investigators

  • Study Director: Jihyun An, MD, PhD, Gastroenterology and Hepatology, Hanyang University College of Medicine, Guri, Republic of Korea

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 28, 2025

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

March 31, 2029

Study Registration Dates

First Submitted

December 31, 2024

First Submitted That Met QC Criteria

February 8, 2025

First Posted (Actual)

February 11, 2025

Study Record Updates

Last Update Posted (Actual)

July 24, 2025

Last Update Submitted That Met QC Criteria

July 21, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024-1524

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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