Clinical trial NCT06971237: SIRT and Peri-immunotherapy : a New Concept
Official title: Response Assessment for Advanced HCC of Combined SIRT and Immunotherapy Treatment
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Advanced Hepatocellular Carcinoma (HCC), Classified as BCLC Stage B or C, Treated With a Combination of Selective Internal Radiation Therapy
Keywords: Hepatocellular Carcinoma
Advanced Liver Cancer
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2025-05-14
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with advanced hepatocellular carcinoma (BCLC stage B or C), not eligible for curative treatments, treated with SIRT and/or immunotherapy

Brief summary: The combination of selective internal radiation therapy (SIRT) with immunotherapy represents an innovative and potentially highly effective therapeutic strategy for the treatment of advanced-stage hepatocellular carcinoma (BCLC stage B or C). Although promising results have been observed in preliminary clinical trials, further research is needed to better understand the underlying mechanisms, optimize treatment protocols, and confirm the long-term efficacy and safety of this combined approach

Detailed description: This retrospective cohort study aims to evaluate the efficacy and safety of a novel combination treatment for advanced hepatocellular carcinoma (HCC), involving Selective Internal Radiation Therapy (SIRT) with Yttrium-90 (Y90) microspheres and peri-immunotherapy (atezolizumab ± bevacizumab) administered in both neoadjuvant and adjuvant settings. The study targets patients with Barcelona Clinic Liver Cancer (BCLC) stage B or C HCC, initially deemed ineligible for curative therapies such as resection, transplantation, or percutaneous ablation.

Recent advances in immunotherapy have shown promise for HCC treatment, but overall response rates remain low due to the immunosuppressive tumor microenvironment. SIRT delivers high-dose localized radiation directly to the tumor, inducing immunogenic cell death and potentially priming the immune system for enhanced response to immune checkpoint inhibitors. This study investigates whether this combination can produce synergistic anti-tumor effects, prolong progression-free survival (PFS) and overall survival (OS), and potentially downstage tumors to make curative treatment feasible.

Data will be retrospectively collected from electronic health records (Orbis), imaging systems (PACS), and pathology databases at the AP-HP GH Paris-Saclay institutions (Hôpital Paul Brousse and Hôpital Bicêtre). A total of 60 patients treated between 2021 and 2024 will be included. Key clinical variables (e.g., age, sex, comorbidities, AFP), imaging response (based on RECIST 1.1, mRECIST, iRECIST, LI-RADS criteria), treatment parameters (e.g., Y90 dose, immunotherapy schedule), histological findings, and adverse events (CTCAE grading) will be systematically extracted and anonymized.

A matched control group of patients treated with immunotherapy alone will be used for comparative analysis. Imaging will be reviewed independently by two senior abdominal imaging radiologists. Statistical analyses will be conducted using R Software (version 3.2.3) in collaboration with the GH Paris-Saclay methodology unit.

This study complies with French and European data protection regulations (MR-004) and has obtained ethical approval from the Bicêtre ethics committee (CER POLETHIS). Patients are informed by mail and included upon non-objection within one month.

The overarching goal is to determine whether the SIRT + peri-immunotherapy protocol offers improved disease control and survival outcomes compared to standard treatment, while maintaining acceptable safety and tolerability.

Eligibility criteria: Inclusion Criteria:

Age ≥ 18 years Diagnosis of hepatocellular carcinoma (HCC) confirmed by imaging or biopsy Tumor \> 6 cm Child-Pugh score A to B7 Not eligible for curative treatment (resection, ablation, transplant, TACE) Macrovascular invasion or AFP \> 100 ng/mL Treated with intra-arterial Yttrium-90 SIRT combined with atezolizumab ± bevacizumab

Exclusion Criteria:

Age \< 18 Non-HCC diagnosis on imaging or pathology Child-Pugh \> B7 Prior immunotherapy or intra-arterial hepatic treatment Under legal guardianship or curatorship

Primary outcomes:
measure: Objective Tumor Response Rate
timeFrame: At 3, 6, 9 and 12 months post-treatment
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: From treatment to disease progression or death, up to 12 months
measure: Overall Survival (OS)
timeFrame: From treatment to death, up to 12 months
measure: Treatment-Related Adverse Events
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: Villejuif
country: France
facility: Hôpital Paul Brousse - Radiology Department
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Paul Brousse
name: Maïté Lewin, Professor
role: PRINCIPAL_INVESTIGATOR
References: