Multinational Phase II Trial to Compare Safety and Efficacy of SIRT (Y-90 Resin Microspheres) Followed by Atezolizumab Plus Bevacizumab, vs SIRT (SIRT-Y90) Followed by Placebo in Locally Advanced HCC Patients

NCT05377034 | Recruiting Phase 2 DMC

• 1 other identifier: AHCC09 STRATUM
• Study Type: interventional
• Target: 100
• Locations: 4 countries
• Sites: 14

Brief Summary

This is a multi-national, phase II, parallel-arm, double-blind, placebo-controlled, two-arm study designed to assess the efficacy and safety of SIRT-Y90 followed by atezolizumab plus bevacizumab \[study arm\], versus SIRT-Y90 followed by placebo \[control arm\] in patients with locally advanced Hepatocellular Carcinoma (HCC).

Conditions

Locally Advanced Hepatocellular Carcinoma

Keywords

SIRT-Y90; Atezolizumab plus Bevacizumab; Hepatocellular Carcinoma; SIR-Sphere

Outcome Measures

Primary Outcomes (1)

• Best Overall Response Rate (BORR) at 9 months post-randomization.

  The number of patients whose Best Overall Response (BOR) at 9 months post-randomization is a partial response or complete response per RECIST v1.1 and mRECIST, divided by the total number of patients in the analysis population.

  9 months post-randomization.

Secondary Outcomes (11)

• Best Overall Response Rate (BORR) at 12-months and 18-months post-randomization.

  12 months and 18 months post-randomization.

• Sustained response rates at 9, 12 and 18 months.

  9,12 and 18 months post-randomization.

• Disease control rates at 9, 12 and 18 months.

  9,12 and 18 months post-randomization.

• Time to response.

  Up to 19 months post-randomization.

• Duration of response (DOR).

  Up to 19 months post-randomization.

Other Outcomes (10)

• SIRT-Y90 post-treatment dosimetry.

  4-week SIRT pre-randomization; 3, 6, 12 and 18 months post-randomization.

• Hepatic progression-free survival (HPFS).

  Up to 19 months post-randomization.

• Tumor resectability rates at 12 and 18 months.

  12 and 18 months post-randomization.

Study Arms (2)

Study Arm

EXPERIMENTAL

SIRT-Y90 + 1200mg atezolizumab + 15mg/kg bevacizumab

Combination Product: SIRT-Y90 with Atezolizumab + Bevacizumab

Control Arm

EXPERIMENTAL

SIRT-Y90 + placebos (IV)

Combination Product: SIRT-Y90 with Placebo (IV)

Interventions

SIRT-Y90 with Atezolizumab + Bevacizumab COMBINATION_PRODUCT

Single or two-staged delivery of SIRT-Y90 (4 to 6 weeks), followed by 1200mg atezolizumab + 15mg/kg bevacizumab administered by IV at every 3 weeks for 18 months.

Study Arm

SIRT-Y90 with Placebo (IV) COMBINATION_PRODUCT

Single or two-staged delivery of SIRT-Y90 (4 to 6 weeks), followed by placebo at every 3 weeks for 18 months.

Control Arm

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must fulfill all of the following criteria to be eligible for this study:
• Unequivocal diagnosis of HCC (AASLD 2010 diagnostic criteria or histology) that is locally advanced without extra-hepatic metastases but with significant tumor burden, i.e.,
• Tumor confined to the liver that is beyond the up-to-7 criteria, and/or
• Tumor with vascular invasion VP 1-3 and/or Vv 1-2 (at the discretion of site investigator) Both local and central assessments are required at screening, prior to any study treatment. Sites are required to send all CT/MRI images for central imaging review. The central assessment result will be made known to sites and will take precedence in determining a patient's study eligibility in case of a discrepancy between local and central review.
• Aged 21 years old and above of either gender.
• Patient eligible for SIRT-Y90 treatment after assessment with macro-aggregated albumin labeled with technetium-99 (Tc-99m MAA) scan on SPECT/CT or planar imaging with all of the following criteria prior to each SIRT-Y90 treatment:
• Lung shunting \<20% on SPECT/CT or planar imaging
• Lung dose limit of \<25Gy for single treatment or \<30Gy for cumulative treatment (second delivery within 4-6 weeks)
• No prior radiation to the liver.
• No prior systemic adjuvant or neoadjuvant therapy for HCC.
• Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥10 mm with spiral CT scan or MRI.
• Negative HIV test at screening, with the following exception - patients with a positive HIV test at screening are eligible provided they fulfil all of the following criteria:
• Are stable on anti-retroviral therapy
• Have a CD4 count ≥ 200/μL
• Have an undetectable viral load

You may not qualify if:

• The following criteria should be checked. If ANY apply, the patient must not be included in the study:
• Patient not eligible for SIRT-Y90 treatment after assessment with macro-aggregated albumin labeled with technetium-99 (MAA) scan on SPECT/CT or planar imaging.
• Patients who have SAE \> grade 3 within 4 weeks after receiving SIRT-Y90. For patients who experience SAE \> grade 3 after receiving SIRT-Y90 (1st or 2nd administration), the duration between the SIRT-Y90 dose and randomization and/or 1st and 2nd SIRT-Y90 dose (for two-staged delivery) may be extended by an additional 4 weeks to re-assess the patient's eligibility.
• Patients who have had \>2 administrations of hepatic artery directed therapy.
• Patients who have had hepatic artery directed therapy done \<4 weeks prior to date of ICF signing.
• Patients who have had systemic adjuvant or neoadjuvant therapy for HCC.
• Prior hepatic radiation therapy for HCC or other malignancy.
• Patient who has received any immunotherapy (including interferon-alfa, peginterferon alfa-2a, peginterferon alfa-2b, thymosin-α1, etc.) within 30 days prior to randomization, is currently receiving immunotherapy or is planned to start immunotherapy during the study (e.g., for the management of active CHB or CHC according to local guidelines).
• Has evidence that \<30% of the total liver volume is disease-free.
• Currently receiving any other investigational agents for the treatment of their cancer.
• Has intractable clinical ascites (in spite of optimal diuretic treatment) or any other clinical signs of liver failure, on physical examination.
• Untreated or incompletely treated esophageal and/or gastric varices prior to randomization.
• Presence of tumor thrombus in the main trunk of the portal vein or a portal vein branch contralateral to the primarily involved lobe (or both) i.e. beyond VP3 and/or tumor thrombus in the inferior vena cava or right atrium i.e. beyond Vv2.
• Any metastatic disease i.e. lymph node ≥15 mm in short axis or distant metastasis.
• Any other concurrent malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for at least five years.

Sponsors & Collaborators

• National Cancer Centre, Singapore: lead
• Hoffmann-La Roche: collaborator
• Sirtex Medical: collaborator
• Singapore Clinical Research Institute: collaborator

Study Sites (14)

Beijing Tsinghua Changgung Hospital

Beijing, China

RECRUITING

People's Liberation Army General Hospital (1st and 6th Medical Centre)

Beijing, China

NOT YET RECRUITING

West China Hospital, Sichuan University

Chengdu, China

RECRUITING

Shandong Cancer Hospital

Jinan, China

NOT YET RECRUITING

National University Hospital

Singapore, 119074, Singapore

RECRUITING

National Cancer Centre Singapore

Singapore, 168583, Singapore

RECRUITING

Samsung Medical Center

Seoul, South Korea

RECRUITING

Seoul National University Hospital

Seoul, South Korea

RECRUITING

Severance Hospital Yonsei University Health System

Seoul, South Korea

RECRUITING

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, Taiwan

RECRUITING

Taichung Veterans General Hospital

Taichung, Taiwan

RECRUITING

National Taiwan University Cancer Center

Taipei, Taiwan

RECRUITING

National Taiwan University Hospital

Taipei, Taiwan

RECRUITING

Taipei Veterans General Hospital

Taipei, Taiwan

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

atezolizumab; Bevacizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Pierce CHOW, MD, PhD

  National Cancer Centre, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Professor Pierce CHOW, MD, PhD

CONTACT

+65 6436 8000; pierce.chow.k.h@singhealth.com.sg

Vennese LOW

CONTACT

+65 6306 5456; low.minxiu.vennese@nccs.com.sg

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This study will be performed in a double-blind manner. The investigators, monitoring team, site staff, and all patients will be blinded to the study treatments from the time of randomization until database lock. Biostatisticians involved in preparing the randomization and safety data analysis for Data and Safety Monitoring Board (independent to study statistician) will be unblinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2022
• First Posted: May 17, 2022
• Study Start: October 26, 2022
• Primary Completion (Estimated): July 25, 2026
• Study Completion (Estimated): January 31, 2028
• Last Updated: October 6, 2025

Record last verified: 2025-09

Locations

CN (4); KR (3); TW (5); SG (2)