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

Sponsor
Chinese University of Hong Kong
Study ID
NCT06823375
Phase
PHASE2
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Radiotherapy — RADIATION
    \- 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.
  • Atezolizumab plus Bevacizumab — DRUG
    \- Atezolizumab 1200mg IV and Bevacizumab 15mg/kg IV will be given every 3 weeks, till disease progression, intolerable toxicity, death or withdrawal of consent.

Study Details

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.

Key Dates

Start date
Jul 10, 2025
Status verified
Mar 2026
Primary completion
Jul 31, 2027
Completion
Jul 31, 2028

Study Design

Enrollment
40 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • 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
  • 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.

Primary Outcome Measure

1-year overall survival (OS) [ Time Frame: 1 year ]

Central Contacts

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