SIRT and Peri-immunotherapy : a New Concept

NCT ID: NCT06971237

Last Updated: 2025-05-14

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Total Enrollment: 60 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-06-01
• Study Completion Date: 2026-07-01

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.

Conditions

Advanced Hepatocellular Carcinoma (HCC), Classified as BCLC Stage B or C, Treated With a Combination of Selective Internal Radiation Therapy

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Interventions

Atezolizumab ± Bevacizumab and Yttrium-90 Radioembolization

Atezolizumab ± Bevacizumab: Peri-immunotherapy with , with or without bevacizumab, given before and after SIRT.

• Yttrium-90 Radioembolization: Selective Internal Radiation Therapy (SIRT) via intra-arterial injection of Yttrium-90 microspheres for liver tumor control

Intervention Type: DRUG

Atezolizumab ± Bevacizumab

Standard systemic immunotherapy administered without SIRT, using atezolizumab with or without bevacizumab.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Maïté Lewin, Professor

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Paul Brousse

Locations

Hôpital Paul Brousse - Radiology Department

Villejuif, , France

Countries

France

Central Contacts

Clara Prud'homme, MD

Role: CONTACT

clara.prudhomme@aphp.fr

0033145212121

Maïté Lewin, Professor

Role: CONTACT

maite.lewin@aphp.fr

0033 1 45 59 39 86

Facility Contacts

Clara Prud'homme, MD

Role: primary

clara.prudhomme@aphp.fr

00 33 1 45 21 33 73

Maïté Lewin, Professor

Role: backup

maite.lewin@aphp.fr

00 33 1 45 59 39 86

Other Identifiers

IDRCB

Identifier Type: OTHER

Identifier Source: secondary_id

APHP241625

Identifier Type: -

Identifier Source: org_study_id