AzTrials
AzTrials

Hepatocellular CarcinomaPhase 2ESCOATNCT06819566

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

A Phase 2 study testing Endoscopic variceal ligation (EVL) in people with Hepatocellular Carcinoma and Esophageal Varix, run by Asan Medical Center at 1 site in South Korea.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 19 to 80 years
What is being tested?
Endoscopic variceal ligation (EVL)
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
1 siteSouth Korea
Study dates
28 May 2025to 31 Mar 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 19 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
  • 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)
Show all 9Show fewer
  • 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.

Who cannot join

  • 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.
Show all 14Show fewer
  • 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:
  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Ju Hyun Shim, MD, PhD contact

+82-2-3010-3190

s5854@amc.seoul.kr

Jiwon Yang, MD contact

+82-2-3010-0452

ryanghyun90@gmail.com

South Korea1 site, 1 recruiting

  • Liver cancer center, Asan Medical Center

    Seoul, Song-pa, 05505

    Ju Hyun Shim, MD, PhD, +82-2-3010-319, s5854@amc.seoul.kr

    Jiwon Yang, MD, +82-2-3010-0452, ryanghyun90@gmail.com

    Recruiting

Other trials in South Korea

About this study

Official title: 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:

Read more

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.

Read the 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.
  1. Study Design
  2. 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.
  1. 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.
  1. 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.

Being tested
Endoscopic variceal ligation (EVL)
Keywords
Hepatocellular carcinoma, Esophageal varix, Bleeding esophageal varices, Endoscopic variceal ligation
Medical subject headings
Carcinoma, Hepatocellular, Esophageal and Gastric Varices

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Endoscopic variceal ligation (EVL)Procedure or surgery

    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.
    1. 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.
Study groups in NCT06819566
Study groupRoleWhat they receive
EVL groupExperimentalThis group is single arm which undergo prophylactic endoscopic variceal ligation for high-risk esophageal varices
Receives: Procedure: Endoscopic variceal ligation (EVL)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The incidence of esophageal variceal bleeding at 6 months

    The incidence of esophageal variceal bleeding at 6 months following treatment in patients with HCC receiving atezolizumab and bevacizumab as standard therapy.

    Measured: 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 outcomes (7)

  1. Cumulative incidence of acute esophageal varix bleeding

    Cumulative incidence of acute esophageal varix bleeding after initiation of Atezo/Bev: acute esophageal varix bleeding is defined as:

    1. 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

    Measured: 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

  2. Cumulative incidence of non-variceal GI bleeding

    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

    Measured: 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

  3. Overall survival

    Overall survival will be evaluated

    Measured: 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

  4. Cumulative incidence of liver-related complications (except for esophageal varix bleeding)

    liver-related complication is defined as ascites, spontaneous bacterial peritonitis, and hepatic encephalopathy

    Measured: 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

  5. Incidence of EVL-related complications

    EVL-related complications will be evaluate after initiation of first EVL

    Measured: 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

  6. Quality of Life Assessment Related to Treatment

    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.

    Measured: Before the date of first EVL, first Atezo/Bev treatment date, and first/third EGD surveillance after first EVL

  7. Development of biomarker predicting occurrence of variceal bleeding and clinical outcome

    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.

    Measured: through 24 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Feb 2025
  2. Study start28 May 2025
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion31 Mar 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
prophylactic EVL for high-risk esophageal varices
Masking
None (open label)
Enrolment
44 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06819566
Sponsor's protocol ID
2024-1524
Acronym
ESCOAT
Status last verified
Jul 2025
First submitted
31 Dec 2024
Last updated
24 Jul 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.

    PubMed 19097774

  • Singal AG, Llovet JM, Yarchoan M, Mehta N, Heimbach JK, Dawson LA, Jou JH, Kulik LM, Agopian VG, Marrero JA, Mendiratta-Lala M, Brown DB, Rilling WS, Goyal L, Wei AC, Taddei TH. AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma. Hepatology. 2023 Dec 1;78(6):1922-1965. doi: 10.1097/HEP.0000000000000466. Epub 2023 May 22. No abstract available.

    PubMed 37199193

  • Ben Khaled N, Moller M, Jochheim LS, Leyh C, Ehmer U, Bottcher K, Pinter M, Balcar L, Scheiner B, Weich A, Leicht HB, Zarka V, Ye L, Schneider J, Piseddu I, Ocal O, Rau M, Sinner F, Venerito M, Gairing SJ, Forster F, Mayerle J, De Toni EN, Geier A, Reiter FP. Atezolizumab/bevacizumab or lenvatinib in hepatocellular carcinoma: Multicenter real-world study with focus on bleeding and thromboembolic events. JHEP Rep. 2024 Apr 8;6(6):101065. doi: 10.1016/j.jhepr.2024.101065. eCollection 2024 Jun.

    PubMed 38798717

  • Ha Y, Kim JH, Cheon J, Jeon GS, Kim C, Chon HJ. Risk of Variceal Bleeding in Patients With Advanced Hepatocellular Carcinoma Receiving Atezolizumab/Bevacizumab. Clin Gastroenterol Hepatol. 2023 Aug;21(9):2421-2423.e2. doi: 10.1016/j.cgh.2022.07.035. Epub 2022 Aug 6. No abstract available.

    PubMed 35944830

  • Song YG, Yeom KM, Jung EA, Kim SG, Kim YS, Yoo JJ. Risk of Bleeding in Hepatocellular Carcinoma Patients Treated with Atezolizumab/Bevacizumab: A Systematic Review and Meta-Analysis. Liver Cancer. 2024 May 22;13(6):590-600. doi: 10.1159/000539423. eCollection 2024 Dec.

    PubMed 39687040

  • Jaiswal V, Jain E, Hitawala G, Loh H, Patel S, Thada P, Nandwana V, Pandey S, Quinonez J, Naz S, Stein JD, Cueva W. Bevacizumab and Sinus Venous Thrombosis: A Literature Review. Cureus. 2021 Nov 11;13(11):e19471. doi: 10.7759/cureus.19471. eCollection 2021 Nov.

    PubMed 34912612

  • Patel JN, Jiang C, Owzar K, Hertz DL, Wang J, Mulkey FA, Kelly WK, Halabi S, Furukawa Y, Lassiter C, Dorsey SG, Friedman PN, Small EJ, Carducci MA, Kelley MJ, Nakamura Y, Kubo M, Ratain MJ, Morris MJ, McLeod HL. Pharmacogenetic and clinical risk factors for bevacizumab-related gastrointestinal hemorrhage in prostate cancer patients treated on CALGB 90401 (Alliance). Pharmacogenomics J. 2024 Mar 4;24(2):6. doi: 10.1038/s41397-024-00328-z.

    PubMed 38438359

  • Cheng AL, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Lim HY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Ma N, Nicholas A, Wang Y, Li L, Zhu AX, Finn RS. Updated efficacy and safety data from IMbrave150: Atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma. J Hepatol. 2022 Apr;76(4):862-873. doi: 10.1016/j.jhep.2021.11.030. Epub 2021 Dec 11.

    PubMed 34902530

  • Larrey E, Campion B, Evain M, Sultanik P, Blaise L, Giudicelli H, Wagner M, Cluzel P, Rudler M, Ganne-Carrie N, Thabut D, Allaire M. A history of variceal bleeding is associated with further bleeding under atezolizumab-bevacizumab in patients with HCC. Liver Int. 2022 Dec;42(12):2843-2854. doi: 10.1111/liv.15458. Epub 2022 Oct 26.

    PubMed 36254617

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Endoscopic variceal ligation (EVL) in people with Hepatocellular Carcinoma and Esophageal Varix, run by Asan Medical Center at 1 site in South Korea.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 24 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Ju Hyun Shim, MD, PhD (+82-2-3010-3190, s5854@amc.seoul.kr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06819566, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in