NCT07122089

Evaluation of SIRT Followed by Immunotherapy for Treatment of Hepatocellular Carcinoma With Portal Vein Thrombosis

A Multicenter Open-label, Prospective Study to Evaluate the Efficacy and Safety of SIRT Using Yttrium-90 Glass Microspheres Followed by Durvalumab and Tremelimumab for Treatment of Hepatocellular Carcinoma With Portal Vein Thrombosis

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Sponsor: Center Eugene Marquis · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, being the third leading cause of cancer-related death worldwide, with approximately 745 000 deaths reported annually. For advanced patients, including patients with tumoral portal vein thrombosis (PVT), most treatment guidelines recommend systemic therapy, either combination immunotherapy (IO) or combination of immunotherapy and anti-angiogenic treatment for first line option. Results for PVT patients are provided in one trial with a median overall survival of 14.2 months with IO underlying the necessity to improve treatment of PVT patients. Two recent other phase 3 trials also reported positive results for different IO regimen. Selective internal radiation therapy (SIRT) using yttrium-90 (90Y)-loaded glass microspheres (TheraSphereTM) can be used for patients with early stage to locally advanced HCC including PVT patients without extrahepatic spread (EHS). TheraSphereTM is recognized and is reimbursed in France for PVT patients without EHS, since 2019.Several retrospective studies have shown promising results for PVT patients. Nowadays use of SIRT in locally advanced HCC is regaining interest based on the results of the randomized DOSISPHERE-01 study including non-operable patients, about 70% with PVT. This randomized Phase II trial using 90Y-loaded microspheres sought was noted the effectiveness of 90Y-loaded microspheres using a personalized dosimetry approach versus a standard dosimetry approach. The use of a systemic treatment as IO after a locoregional treatment with the strong local debulking effect of SIRT is logical and of interest. Indeed, the most frequent pattern of progression after SIRT is recurrence in an untreated area, including untreated liver or EHS. Patients are then usually referred to IO. Such kind of therapeutic approach, using SIRT followed by IO has already been evaluated in a phase 2 study using nivolumab after 90Y loaded resin microspheres with promising efficacy without safety deterioration. The aim of this study is to evaluate SIRT followed by IO used according to their current indications in advanced HCC patient with PVT patients and without EHS.

Detailed description

The study plans to included 80 patients and to treated 72 patients (take into account screen failures and SIRT contraindications). First, patient will receive SIRT using Yttrium-90 glass microspheres. Immunotherapy with an injection of Tremelimumab followed by Durvalumab must be started 1 to 3 weeks after SIRT. Durvalumab monotherapy is continued every 4 weeks until disease progression, or toxicity leading to definitive treatment discontinuation, or loss of clinical benefit, or investigator decision, or lost for follow-up or death patient. Patients are followed prior to the occurrence of progressive disease, within a maximum 18-month period after the initiation IO.

Conditions

• Hepatocellular Carcinoma Non-resectable

Interventions

Type	Name	Description
DEVICE	Selective Internal Radiotherapy	SIRT will use Yttrium-90 glass-microspheres (TheraSphereTM). SIRT needs two steps: the treatment simulation (diagnostic angiography and scintigraphy of hepatic perfusion with 99mTc-MAA) and the administration (during a therapeutic angiography).
DRUG	Tremelimumab	Tremelimumab should be done 1 to 3 weeks after SIRT and is administrated according to the Summary of Product Characteristic (SPC).
DRUG	Durvalumab	After the end of the tremelimumab infusion, patient receive durvalumab then one injection every 4 weeks until further progression upon investigator decision. Also administrated according to the Summary of Product Characteristic (SPC).

Timeline

• Start date: 2026-01-02
• Primary completion: 2030-01-02
• Completion: 2030-01-02
• First posted: 2025-08-14
• Last updated: 2025-08-14