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

Sponsor
Center Eugene Marquis
Study ID
NCT07122089
Phase
PHASE2
Status
Recruiting
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Conditions

  • Hepatocellular Carcinoma Non-resectable

Eligibility Criteria

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

Interventions

  • Selective Internal Radiotherapy — DEVICE
    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).
  • Tremelimumab — DRUG
    Tremelimumab should be done 1 to 3 weeks after SIRT and is administrated according to the Summary of Product Characteristic (SPC).
  • Durvalumab — DRUG
    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).

Study Details

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.

Key Dates

Start date
Feb 25, 2026
Status verified
Aug 2025
Primary completion
Jan 2, 2030
Completion
Jan 2, 2030

Study Design

Enrollment
80 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Hepatocellular carcinoma with portal vein thrombosis and without hepatic spread
    Patient will receive selective internal radiation therapy and immunotherapy as per standard of care. SIRT Administration is direct intra-arterial injection in the hepatic artery to target only liver disease and IO will be performed as describe below: * Tremelimumab (Imjudo®): 300 mg IV, one-hour infusion; * Durvalumab (Imfinzi®): 1500 mg IV, one-hour infusion every 4 weeks.

Primary Outcome Measure

Objective Response Rate (ORR) [ Time Frame: Through study completion, an average of 4 years ]

Central Contacts

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