A Study Evaluating the Safety and Efficacy of Selective Internal Radiation Therapy (SIRT) Using SIR-Spheres® Y-90 Resin Microspheres to Bridge or Downstage Patients With Hepatocellular Carcinoma (HCC) to Liver Transplant or Resection and Elicit Pathologic Necrosis.

NCT07663487 | Not Yet Recruiting Phase 2 DMC FDA Device

• 1 other identifier: STX-A-206-U (GEMINY-90)
• Study Type: interventional
• Target: 78
• Locations: 0 countries
• Sites: N/A

Brief Summary

This clinical investigation involves the use of an approved medical device (SIR-Spheres®) for a new purpose in patients with certain types of liver cancer. The goal is to determine whether this treatment can help patients qualify for or maintain eligibility for a liver transplant. Participation is completely voluntary and will not affect your standard medical care. The main risks involve possible side effects related to the use of radiation in the liver, such as fatigue, abdominal pain, nausea, or changes in liver function. You may or may not benefit personally from participating in this study, but the results may help improve future treatment for others. Your doctor is inviting you to take part in this clinical investigation because you have been diagnosed with liver cancer. Your doctors will have decided that treatments designed to remove or destroy cancer completely, such as surgery or heat treatment, are not suitable for you. This clinical investigation is focused on testing how well selective internal radiation therapy (SIRT) using SIR-Spheres® Y-90 resin microspheres ("SIR-Spheres") work, its potential benefits, its safety, and finding out if there are any bad effects when it's used like it's supposed to be used. For more information, please see the section on the purpose of the clinical investigation. This Patient Informed Consent Form (PIC) tells you about the clinical investigation. It explains the tests and treatments involved and how your information will be used. Knowing what is involved will help you decide if you want to take part in the clinical investigation.

Conditions

Hepatocellular Carcinoma (HCC)

Outcome Measures

Primary Outcomes (1)

• To determine the proportion of subjects in both cohorts eligible for liver transplant or resection through 6 months following treatment with SIR-Spheres Y-90 resin microspheres.

  Downstaging Cohort: • The proportion of subjects that reach transplant eligibility or resection through 6 months following treatment with SIRSpheres Y-90 resin microspheres. Anatomical resection may be considered for larger, single tumors if adequate remnant liver volume (\>40% for cirrhosis) is preserved and well-compensated function. Bridging Cohort: • The proportion of subjects that maintain transplant eligibility or resection through 6 months following treatment with SIRSpheres Y-90 resin microspheres. Anatomical resection may be considered for larger, single tumors if adequate remnant liver volume (\>40% for cirrhosis) is preserved and well-compensated function per multidisciplinary team.

  6mth Efficacy, 15mth Safety

Study Arms (1)

Treatment Arm: Two-Cohort

EXPERIMENTAL

Participants, who are candidates for bridging or downstaging to liver transplantation using SIRT with SIR-Spheres® Y-90 resin microspheres, will be treated under one of two cohorts: * Bridging Cohort: Patients with unresectable HCC meeting Milan criteria, defined as either a solitary tumor ≤5 cm or up to 3 lesions each ≤3 cm, without extrahepatic disease or vascular invasion. * Downstaging Cohort: Patients with unresectable HCC meeting United Network of Organ Sharing (UNOS) downstaging criteria, defined as either a solitary tumor measuring 5-8 cm, 2-3 tumors each ≤5 cm with a combined tumor diameter ≤8 cm, or 4-5 tumors each ≤3 cm with a combined tumor diameter ≤8 cm, without extrahepatic disease or vascular invasion. Eligible patients must not be considered suitable for curative treatment by resection or ablation at the time of study entry, in the opinion of the investigator.

Device: SIR-Spheres Selectively Delivered to Liver Tumor

Interventions

SIR-Spheres Selectively Delivered to Liver Tumor DEVICE

SIRT involves the following two procedural components: 1. Embolization: Injection into the distal arterial tumor feeding vessels of microspheres (SIR-Spheres), which act as the delivery vehicle for the therapeutic moiety Y-90, and 2. Irradiation: Once located in the distal microvasculature of the tumor, SIRSpheres deliver high dose beta irradiation to the tumor microvascular plexus and to tumor cells directly.

Treatment Arm: Two-Cohort

Eligibility Criteria

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

You may qualify if:

• Willing, able, and mentally competent to provide written informed consent
• Age 18 years or older at the time of informed consent
• All tumors must be measurable by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) according to localized mRECIST
• Diagnosis of HCC with Liver Imaging Reporting and Data System (LIRADS) 5 or by histology that is amenable to treatment with Y-90 radioembolization by radiation segmentectomy
• Patients must be treatment-naïve or have developed a new lesion following one of the prior locoregional treatments listed below, including TACE failure, as defined by the investigator:
• Liver resection with negative pathologic margins, no vascular invasion, and no recurrence at resection margins for at least 6 months post-treatment and no new lesions within 6 months of liver resection
• Ablation of a single ≤3 cm lesion with no recurrence of the treated lesion for at least 6 months post-treatment
• Trans-arterial chemoembolization (TACE) failure or refractoriness (e.g., inadequate response or progression following TACE), per investigator assessment
• Bridging Cohort:
• Unresectable HCC within Milan criteria for liver transplant at baseline (Mazzafero et al, 1996) \[17\]
• Solitary tumor ≤5 cm or up to 3 lesions each ≤3 cm
• No EHD
• No vascular involvement
• Downstaging Cohort:
• Unresectable HCC within UNOS downstaging criteria for liver transplant at baseline (Natarajan et al, 2023) \[21\]

You may not qualify if:

• Eligible for curative treatment by resection or not considered optimal candidates for curative ablation, in the opinion of the investigator, based on tumor location, multifocality, underlying liver disease, anticipated risk of recurrence, or institutional practice patterns.
• Prior systemic anti-cancer therapy (including immunotherapy and/or targeted therapy), radiotherapy or use of other investigational agents for the treatment of HCC
• Intrahepatic arteriovenous shunting (arteriovenous shunting resulting from a biopsy is allowed but must be embolized during the pre-treatment mapping procedure)
• History of biliary-enteric anastomosis (e.g., hepaticojejunostomy) or active biliary infection (e.g., ongoing cholangitis) at the time of screening. Subjects with prior biliary intervention (e.g., Endoscopic Retrograde Cholangiopancreatography (ERCP), sphincterotomy, biliary stent placement) or suspected compromise of the Ampulla of Vater may be enrolled at the Investigator's discretion provided there is no evidence of active biliary infection and prophylactic antibiotic coverage is administered per institutional standard of care before and after Y-90 radioembolization.
• Planned localized cancer treatment to the liver, other than the study treatment, throughout the duration of the study
• Planned systemic cancer treatment throughout the duration of the study
• Portal vein tumor thrombosis (macrovascular invasion). Bland (non-tumoral) portal vein thrombosis is allowed if portal venous flow is preserved and there is no evidence of clinically significant portal hypertension complications that would increase risk of hepatic decompensation.
• Patients with EHD
• Patients with contraindications to angiography or selective visceral catheterization
• Evidence of extrahepatic collateral supply to the tumor
• Evidence of potential delivery of mean radiation dose \>30 Gy to the lungs (single treatment)
• Evidence of any detectable 99mTc-MAA scintigraphy or cone-beam computed tomographic (CB-CT) evidence of any deposition outside of the liver in the gastrointestinal tract after application of established angiographic techniques to stop or mitigate such flow (e.g., placing catheter distal to gastric vessels or coiling)
• mTc-MAA hepatic arterial perfusion scintigraphy showing poor tumor and/or portal vein thrombosis targeting that would lead to a dose that does not meet the liver dosing criteria.
• Female patients who are pregnant, breastfeeding, or pre-menopausal and unwilling to use an effective method of contraception through the 1-year followup; males unwilling to use an effective method of contraception for 30 days post-procedure
• Evidence of portal hypertension with uncontrolled or refractory ascites despite optimal medical management or any active or uncontrolled variceal bleeding at the time of screening

Sponsors & Collaborators

• Sirtex Medical: lead

MeSH Terms

Conditions

Carcinoma, Hepatocellular

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

Study Officials

• David Wootten, PhD

  Sirtex Medical

  STUDY CHAIR

Central Study Contacts

Christopher Gunter Gunter, MPH

CONTACT

9015962386; christopher.gunter@sirtex.com

Dave Wootten Wootten, PhD

CONTACT

9015962386; david.wootten@sirtex.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Two Cohort Study

Study Record Dates

• First Submitted: June 16, 2026
• First Posted: June 23, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): October 1, 2029
• Last Updated: June 25, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share