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

NCT06819566 | Recruiting Phase 2 DMC

• 1 other identifier: 2024-1524
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief 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. 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. 1.Undergo prophylactic EVL before starting Atezo/Bev therapy (within 2 weeks ± 1 week before the first dose).
2. 2.Start Atezo/Bev therapy 2 weeks (± 1 week) after EVL.
3. 3.Have follow-up endoscopies (EGD) one week after the 3rd, 5th, and 7th doses of Atezo/Bev.

Conditions

Hepatocellular Carcinoma; Esophageal Varix; Bleeding Esophageal Varices

Keywords

Hepatocellular carcinoma; Esophageal varix; Bleeding esophageal varices; Endoscopic variceal ligation

Outcome Measures

Primary Outcomes (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.

  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)

• 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 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

• 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

• 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

Study Arms (1)

EVL group

EXPERIMENTAL

This group is single arm which undergo prophylactic endoscopic variceal ligation for high-risk esophageal varices

Procedure: Endoscopic variceal ligation (EVL)

Interventions

Endoscopic variceal ligation (EVL) PROCEDURE

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.

EVL group

Eligibility Criteria

• Age: 19 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Asan Medical Center: lead
• Seoul National University Hospital: collaborator
• Hanyang University: collaborator
• Samsung Medical Center: collaborator
• National Cancer Center, Korea: collaborator
• Seoul National University Bundang Hospital: collaborator

Study Sites (1)

Liver cancer center, Asan Medical Center

Seoul, Song-pa, 05505, South Korea

RECRUITING

Related Publications (9)

• 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.

  PMID: 19097774 RESULT

• 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.

  PMID: 37199193 RESULT

• 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.

  PMID: 38798717 RESULT

• 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.

  PMID: 35944830 RESULT

• 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.

  PMID: 39687040 RESULT

• 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.

  PMID: 34912612 RESULT

• 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.

  PMID: 38438359 RESULT

• 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.

  PMID: 34902530 RESULT

• 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.

  PMID: 36254617 RESULT

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Esophageal and Gastric Varices

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Esophageal Diseases; Gastrointestinal Diseases; Hypertension, Portal

Study Officials

• Jihyun An, MD, PhD

  Gastroenterology and Hepatology, Hanyang University College of Medicine, Guri, Republic of Korea

  STUDY DIRECTOR

Central Study Contacts

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: prophylactic EVL for high-risk esophageal varices

Study Record Dates

• First Submitted: December 31, 2024
• First Posted: February 11, 2025
• Study Start: May 28, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): March 31, 2029
• Last Updated: July 24, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)