Proton Beam Radiotherapy Followed by Tecentriq and Avastin for Primary Liver Cancer With Vp2-4 Portal Vein Invasion

NCT05625893 | Completed Phase 2 DMC

• 1 other identifier: PORTAL
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief Summary

This study is investigator initiated, single-institution, prospective, phase 2 open-label study to determine the efficacy and safety of combination therapy of atezolizumab/bevacizumab and proton beam therapy to portal vein tumor thrombosis with or without main primary tumor in patients with stage 3 or higher hepatocellular carcinoma (HCC) with Vp2-4 portal vein invasion who had not undergone systemic therapy for HCC. The primary endpoint of this study is progression-free survival and secondary endpoints are overall survival (OS), time to progression (TTP), objective response rate, disease control rate (DCR), and time to local disease progression (LTP).

Conditions

Hepatocellular Carcinoma; Portal Vein Thrombosis

Outcome Measures

Primary Outcomes (2)

• Progression-free survival rate

  At 9 month

• Incidence of adverse event assessed according to the Common Terminology Criteria for Adverse Events (CTCAE version 5.0)

  From date of atezolizumab and bevacizumab initiatton until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months

Secondary Outcomes (5)

• Overall survival rate

  At 12 month

• Time-to-progression

  At 9 months

• Objective response rate

  At 3 month

• Disease Control rate

  At 3 month

• Local tumor progression rate

  At 12 month

Study Arms (1)

PBT arm

EXPERIMENTAL

Radiation: PBT and atezolizumab/bevacizumab

Interventions

PBT and atezolizumab/bevacizumab RADIATION

Atezolizumab 1200 mg and bevacizumab 15 mg/Kg is administered IV infusion every 3 weeks. Proton beam therapy 30 - 50 Gy/5 fractions to portal vein tumor thrombosis with or without main primary tumor after 1 week (+/- 7 days) of 2nd cycle of atezolizumab and bevacizumab The follow-up phase begins when the decision to discontinue study is made. The follow-up phase is defined as the day after the end of study treatment until the day the subject dies.

PBT arm

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with HCC meeting all of following criteria;
• Histologically or radiologically confirmed hepatocellular carcinoma based on the guidelines of the Korean Liver Cancer Association-National Cancer Center 2022
• Age \>= 20
• Vp2-4 portal vein tumor thrombosis diagnosed by dynamic enhanced computed tomography (CT) or maganetic resonance images (MRI) with below finding 1) an intraluminal filling defect adjacent to the primary tumor in Vp2-4 portal vein 2) an enhancement of the filling defect on arterial phase and a washout on portal/delayed phases.
• Signed written informed consent
• at least one or more measurable intrahepatic viable HCC lesions
• Child-Pugh class A within 2 weeks from screening for study registration
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1 within 2 weeks from screening for study registration
• Life expectancy of at least 16 weeks
• adequate bone marrow and liver function within 2 weeks from screening for study registration
• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1,000/mm3
• Platelet count ≥ 50,000/μL
• Total bilirubin \< 2.5 mg/dL
• Serum albumin \>2.8 g/dL

You may not qualify if:

• no limitation according to the size and number of tumors in the liver.
• Patients with HCC meeting all of following criteria;
• previous history of systemic treatment for HCC (If systemic treatment for HCC has been performed at least once, it will not be enrolled in this study.) However, registration is permitted if the previous systemic treatment is for adjuvant purposes or treatment for other cancers. Also allowed if previous HCC treatment is local treatment. However, cases with a history of previous upper abdominal radiotherapy (including proton therapy and heavy particle therapy) are excluded.
• any type of anticancer agent (including investigational) within 2 weeks before enrollment
• Having active brain metastasis or leptomeningeal metastasis need surgery or steroid therapy
• Moderate to severe or intractable ascites
• A history or presence of hepatic encephalopathy
• Presence of active bacterial infection
• Untreated active chronic hepatitis B or active hepatitis C
• History of portal hypertension with bleeding within the past 6 months
• Prior liver transplant
• Uncontrolled severe medical comorbidity
• unhealed wound
• uncontrolled electrolyte imbalance
• Non-interruptible therapeutic use of anticoagulants or thrombolytics

Sponsors & Collaborators

• Samsung Medical Center: lead

Study Sites (1)

Samsung Medical Center

Seoul, 06351, South Korea

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

atezolizumab; Bevacizumab

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jeong Il Yu, MD, PhD

  Samsung Medical Center

  PRINCIPAL INVESTIGATOR

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: Assistant Professor

Study Record Dates

• First Submitted: September 20, 2022
• First Posted: November 23, 2022
• Study Start: January 15, 2023
• Primary Completion: November 30, 2025
• Study Completion: March 30, 2026
• Last Updated: April 23, 2026

Record last verified: 2026-04

Locations

KR (1)