SBRT With Immunotherapy and Atezo-Bev in HCC With Major Portal Vein Thrombosis

Stereotactic Body Radiotherapy With Immunotherapy (Atezolizumab Plus Bevacizumab) in Patients With Advanced HCC and Major Portal Vein Tumour Thrombosis

Patients with PVTT involvement is a significant healthcare burden as they are present in up to 40% of patients with HCC at diagnosis. These patients exhibit a poorer prognosis compared to patients without PVTT, as a result they were often excluded from existing pivotal clinical trials [9-11]. Without management, the median OS in affected patients could be as short as 2 to 4 months. The role of liver-directed therapies is limited for patients with major PVTT. For example, percutaneous ablation to PVTT is technically challenging, especially for centrally located PVTT due to their proximity to hepatic vasculature and bile ducts. Transarterial therapies are contraindicated for patients with major PVTT due to risk of concurrent interruption of both hepatic arterial and portal venous blood flow resulting in severe liver ischemia. Therefore, patients with major PVTT are recommended to receive systemic treatment by international guidelines. Yet, the OS for patients with main PVTT remained poor. In the exploratory analysis of IMbrave-150, patients with main PVTT who received atezolizumab plus bevacizumab had a median OS of 7.6 months only, compared to 21.1 months for those without PVTT. There is a huge unmet for this group of patients with dismal prognosis.

SBRT is a radiotherapy technique that enables delivery of high dose of radiation in an extremely precise manner. Compared to more conventional radiotherapy techniques such as intensity modulated radiotherapy (IMRT), SBRT has the advantage of superior disease control, minimizing dose to normal tissue and toxicity, and reduction of overall treatment time. For patients with PVTT, a number of retrospective and prospective trials have shown that SBRT can offer durable local control for patients with PVTT involvement. For instance, a randomized trial conducted in Korean which compared the combination of TACE-radiation (TACE-RT) with sorafenib, involving 90 patients with Child-Pugh A HCC with macrovascular invasion (MVI) (35% had main or bilateral portal vein involvement), showed improved 12-week PFS (86.7% vs. 34.3%), time-to-progression (31.0 vs. 11.7 weeks; p<0.001), and OS (55.0 vs. 43.0 weeks; p=0.04) with TACE-RT. In a Canadian single-center retrospective study including 128 patients with HCC and MVI treated with SBRT between 2003 to 2016, 1-year local control was 87.4% and median OS was 18.3 months.

Given the existing evidence, it would be of interest to study the efficacy and safety of atezolizumab plus bevacizumab and SBRT to portal venous tumour thrombosis in this patient group.

Study Overview

• Status: Recruiting
• Conditions: HCC
• Intervention / Treatment: Radiation: Radiotherapy; Drug: Atezolizumab plus Bevacizumab

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Landon CHAN; Phone Number: 3505 1042; Email: landon.chan@cuhk.edu.hk
• Study Contact Backup: Name: Natalie KWONG; Phone Number: 3505 1040; Email: nataliekwong019@cuhk.edu.hk

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • Department of Clinical Oncology, Prince of Wales Hospital
    • Contact: Natalie KWONG; Phone Number: 3505 1040; Email: nataliekwong019@cuhk.edu.hk
    • Contact: Landon L CHAN; Phone Number: 3505 1042; Email: landon.chan@cuhk.edu.hk
    • Principal Investigator: Landon L CHAN
  • Hong Kong, Hong Kong
    • Recruiting
    • Department of Clinical Oncology, Tuen Mun Hospital
    • Contact: Natalie SM WONG; Phone Number: 2468 5088; Email: wsm011@ha.org.hk
    • Contact: Jay JJ Huang; Phone Number: 2468 5088; Email: hjj732@ha.org.hk
    • Principal Investigator: Natalie SM WONG

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients aged ≥ 18 years old
• ECOG performance 0 to 1
• Confirmed diagnosis of HCC (either histologic or cytologic analysis, or clinical features according to the American Association for the Study of Liver Diseases)
• Presence of major portal vein thrombosis (Vp3 [first-order tumour thrombosis in portal vein] or Vp4 [tumour thrombosis in the main portal vein, or portal vein branch in contralateral lobe]), limited to the liver and should be amenable to SBRT
• No disease progression after 2 cycles of atezolizumab plus bevacizumab
• Presence of ≤5 lesions within the liver
• Gastric or esophageal varices must be screened; if interventions were performed, repeated upper endoscopy is needed to confirm healing of treated varices
• Child-Pugh A liver function
• Life expectancy longer than 3 months
• At least one measurable treatment lesion according to RECIST 1.1
• Extrahepatic metastases are allowed, limited to 3 sites, and not causing functional compromise
• Written informed consent must be obtained prior to any study related procedures
• Adequate haematological function (Hb ≥ 8.5g/dL; Plt ≥ 75x109/L; ANC ≥ 1.5x109/L; INR ≤ 1.5)
• Adequate hepatic function (albumin ≥ 28g/L; Bilirubin ≤ 40 μmol/L; ALT < 5 times upper limit normal)
• Adequate renal function (serum creatinine ≤ 2 times the upper limit of normal range; Na ≥ 130mmol/L; K ≥ 3.0mmol/L)
• Able to read, understand and provide written consent

Exclusion Criteria:

• History of another malignancy except appropriately-treated BCC of skin or CIN of cervix during the last 5 years
• History of rupture HCC in the past 3 months
• History of gastric or esophageal varices with interventions performed within 1 month
• Tumour thrombosis that extends beyond the portal vein (e.g. inferior vena cava, superior vena cava)
• Liver tumours occupy ≥ 50% of liver
• Previous radiotherapy to the abdomen
• Previous yttrium-90 chemoembolization
• Repetitive history of non-healing wounds or ulcers within 2 months of inclusion
• Pregnant or lactating females at any time during the study
• Active autoimmune disease requiring systemic therapy in the past 2 years
• Diagnosis of immunodeficiency (including HIV)
• Ongoing corticosteroid therapy >10mg prednisone daily

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Receiving Atezolizumab + Bevacizumab and SBRT; In the experimental arm, Atezolizumab 1200mg IV and Bevacizumab 15mg/kg IV will be given every 3 weeks, till disease progression, intolerable toxicity, death or withdrawal of consent.; SBRT 27.5Gy to 50Gy in 5 fractions on alternate days will be delivered between cycle 3 and 5 to the PVTT and its adjacent lesions.; Bevacizumab will be withhold 4 weeks before and after SBRT to avoid potential interaction with radiotherapy that may potentiate treatment-related toxicity	Radiation: Radiotherapy; - SBRT 27.5Gy to 50Gy in 5 fractions on alternate days will be delivered between cycle 3 and 5 to the PVTT and its adjacent lesions.; Other Names: Stereotactic Body Radiation Therapy (SBRT)
Other: Standard of care Atezolizumab + Bevacizumab alone (Control arm); - In the control arm, Atezolizumab 1200mg IV and Bevacizumab 15mg/kg IV will be given every 3 weeks, till disease progression, intolerable toxicity, death or withdrawal of consent.	Drug: Atezolizumab plus Bevacizumab; - Atezolizumab 1200mg IV and Bevacizumab 15mg/kg IV will be given every 3 weeks, till disease progression, intolerable toxicity, death or withdrawal of consent.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
1-year overall survival (OS)	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Median overall survival (OS)	2 years
Median progression-free survival (PFS)	2 years
Objective response rates (RECIST 1.1)	2 years
Treatment related adverse events	2 years

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2025
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2028

Study Registration Dates

• First Submitted: February 6, 2025
• First Submitted That Met QC Criteria: February 10, 2025
• First Posted (Actual): February 12, 2025

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: March 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: SBRT in HCC; major portal vein thrombosis
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Embolism and Thrombosis; Thrombosis; Amino Acids, Peptides, and Proteins; Proteins; Investigative Techniques; Therapeutics; Surgical Procedures, Operative; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Stereotaxic Techniques; Neurosurgical Procedures; Bevacizumab; Radiotherapy; Radiosurgery; atezolizumab
• Other Study ID Numbers: HCC080

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
• product manufactured in and exported from the U.S.: No