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

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

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).

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma; Portal Vein Thrombosis
• Intervention / Treatment: Radiation: PBT and atezolizumab/bevacizumab

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 2

Contacts and Locations

Study Locations

• South Korea
  • Seoul, South Korea, 06351
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with HCC meeting all of following criteria;

  1. Histologically or radiologically confirmed hepatocellular carcinoma based on the guidelines of the Korean Liver Cancer Association-National Cancer Center 2022
  2. Age >= 20
  3. 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.
  4. Signed written informed consent
  5. at least one or more measurable intrahepatic viable HCC lesions
  6. Child-Pugh class A within 2 weeks from screening for study registration
  7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1 within 2 weeks from screening for study registration
  8. Life expectancy of at least 16 weeks

  9. 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

               • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 × upper limit of normal (ULN)

                 • Prothrombin time in INR ≤ 1.8 × ULN

                   • Serum creatinine ≤ 1.5 mg/dL
  10. Women of childbearing potential and men must agree to use highly efficient contraception since signing of the informed consent form until at least 6 months (women) and 7 months (men) after the last study drug administration
  11. If other selection conditions are satisfied and the exclusion criteria are not met, registration is possible even in case of N1 or M1.
  12. Registration is possible even in the case of hepatic vein tumor infiltration if other selection conditions are satisfied and the exclusion criteria are not met
  13. no limitation according to the size and number of tumors in the liver.

Exclusion Criteria:

Patients with HCC meeting all of following criteria;

1. 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.
2. any type of anticancer agent (including investigational) within 2 weeks before enrollment
3. Having active brain metastasis or leptomeningeal metastasis need surgery or steroid therapy
4. Moderate to severe or intractable ascites
5. A history or presence of hepatic encephalopathy
6. Presence of active bacterial infection
7. Untreated active chronic hepatitis B or active hepatitis C
8. History of portal hypertension with bleeding within the past 6 months
9. Prior liver transplant
10. Uncontrolled severe medical comorbidity
11. unhealed wound
12. uncontrolled electrolyte imbalance
13. Non-interruptible therapeutic use of anticoagulants or thrombolytics
14. History of uncontrolled or autoimmune disease, or immunocompromised
15. interstitial lung disease
16. Other malignant disease (a history of treated malignancy -other than HCC- is allowable if the patient's malignancy has been in complete remission, off chemotherapy and without additional surgical intervention, during the preceding two years)
17. Mentally retarded/medically incapable of consent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: PBT arm

Radiation: PBT and atezolizumab/bevacizumab; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Investigators: Principal Investigator: Jeong Il Yu, MD, PhD, Samsung Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2023
• Primary Completion (Actual): November 30, 2025
• Study Completion (Actual): March 30, 2026

Study Registration Dates

• First Submitted: September 20, 2022
• First Submitted That Met QC Criteria: November 15, 2022
• First Posted (Actual): November 23, 2022

Study Record Updates

• Last Update Posted (Actual): April 23, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Bevacizumab; atezolizumab
• Other Study ID Numbers: PORTAL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No