Efficacy and Safety of Yttrium-90 Microspheres Selective Internal Radiotherapy Combined with Immune Checkpoint Inhibitors and Anti-angiogenesis Drugs Sequential HAIC for Hepatocellular Carcinoma

NCT06867432 | Not Yet Recruiting Phase 2

• 1 other identifier: EC-2025-0003
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

To observe and evaluate the efficacy and safety of selective internal radiotherapy (SIRT) based on transarterial radioembolization with yttrium (90Y) microspheres combined with immune checkpoint inhibitors and anti-angiogenic-drug sequential hepatic arterial infusion chemotherapy (HAIC) for the treatment of initially unresectable hepatocellular carcinoma with transformation potential.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• ORR mRESIST

  from the date of enrollment to death from any cause.

  Prior to surgery

Secondary Outcomes (5)

• Transformation success rate

  Up to approximately 48 months

• R0 Resection Rate

  Up to approximately 48 months

• Progression-free survival (PFS)

  Up to approximately 48 months

• Overall survival (OS)

  Randomization to death from any cause (up to approximately 3 years)

• Pathologic Complete Response (pCR) Rate

  Up to approximately 48 months

Study Arms (1)

SIRT-Y90+HAIC+PD-1 or PD-L1 inhibitors +targeted therapy

EXPERIMENTAL

Yttrium (90Y) -SIRT treatment: SIRT enables resin-based yttrium (90Y) microspheres. The radioactivity of yttrium (90Y) and the therapeutic dose were calculated by the body surface product method. The designated dose of yttrium (90Y) microsphere injection was infused after hepatic arterial catheterization, tumor donor artery. The treatment sessions targeted the liver lobe with a larger tumor volume. Patients were monitored for 2 days after treatment. In cases of local tumor progression and contraindications, SIRT may be repeated. Hepatic arterial infusion chemotherapy: specific drug dose, drug method according to current guidelines and drug marketing instructions. Every 3 weeks starting after 3 weeks of yttrium (90Y) -SIRT. PD-L1/PD-1 inhibitors and targeted therapy as specified in the guidelines are allowed to be administered during each treatment

Drug: Combination Product：t: SIRT-Y90 +HAIC+Atezolizumab + Bevacizumab

Interventions

Combination Product：t: SIRT-Y90 +HAIC+Atezolizumab + Bevacizumab DRUG

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. HAIC：administration of oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries every 3 weeks.

SIRT-Y90+HAIC+PD-1 or PD-L1 inhibitors +targeted therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 and ≤75 years of age, regardless of gender;
• Hepatocellular carcinoma (HCC) diagnosed clinically or pathologically with the following characteristics and assessed by the investigator to be initially not amenable to surgical resection but with the potential for surgical resection after conversion therapy;
• The tumour is confined to a unilateral hepatic lobe, with no extrahepatic metastases and no clinical evidence of high pressure on the imperial vein;
• CNLC stage Ib-IIIa;
• ECOG PS score: 0-1;
• At least one measurable lesion according to mRECIST criteria;
• Child-Pugh A;
• For patients with active hepatitis B virus (HBV): HBV-DNA must be \<2,000 IU/mL and must have received at least 14 days of anti-HBV treatment (based on current guidelines, e.g., entecavir) prior to the start of study treatment and be willing to receive antiviral treatment for the full duration of the study; HCV-RNA-positive patients must receive antiviral treatment according to guidelines; and HCV-RNA-positive patients must receive antiviral treatment according to guidelines. HCV-RNA-positive patients must be receiving antiviral therapy according to guidelines and have liver function within CTCAE class 1 ascending;
• No severe fluid, renal, or coagulation dysfunction:
• Gynecological examination (excluding the use of any gynecological fluid component and cell growth within 14 days) 1) Neutrophil count (NE) \>1.5 x 109/L; 2) Glucose count (NE) \>1.5 x 109/L; 3) Glucose count (NE) \>1.5 x 109/L; 2) Hemoglobin count (HGB) \>90 g/L; 3) Platelet count (PLT) \>75×109/L;
• Liver and kidney function:
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• Serum creatinine ≤2.0×ULN;
• Total bilirubin (TBIL) ≤ 2.0 × ULN;
• Aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 × ULN;

You may not qualify if:

• Known fibroplaque HCC, hydatidiform HCC, or mixed hepatocellular carcinoma;
• Refractory ascites (despite optimal diuretic therapy) or any other clinical signs of liver failure;
• Untreated or incompletely treated hydronephrosis and/or fundal varices or those at high risk of bleeding as assessed by the investigator, or a history of bleeding due to hydronephrosis or fundal varices within 1 month prior to entry;
• Major surgical treatment or chemotherapy, radiotherapy or other systemic treatment of the lesion within 1 month prior to entry;
• Previous allogeneic nickel-hydride cell or solid organ transplantation;
• Active autoimmune disease requiring systemic therapy (use of palliative medications, steroids, or immunosuppressants); or Thymosin-α1, etc.) within 30 days of the study.
• Have received a live attenuated vaccine within 4 weeks prior to the study, or expect to receive such a vaccine during treatment or within 5 months of the last dose.
• Uncontrolled medical conditions including, but not limited to, persistent infections (other than viral hepatitis), symptomatic cardiac failure, unstable heartburn, colic, cardiac arrest, and heartburn.Uncontrolled medical conditions include, but are not limited to, persistent infections (except viral hepatitis), symptomatic cardiac failure, unstable cardiac colic, irregular heartbeat or severe mental illness;
• Uncontrolled high blood pressure (systolic \> 150 mmHg and/or diastolic \> 100 mmHg). 10. other active malignant tumours;
• Other active malignancies (completely resected basal cell carcinoma, stage I squamous cell carcinoma, carcinoma in situ, intramucosal carcinoma, and superficial bladder cancer).Other active malignancies (except completely resected basal cell carcinoma, stage I squamous cell carcinoma, carcinoma in situ, intramucosal carcinoma, and superficial bladder carcinoma, and any other cancer that has not recurred for at least 5 years);
• A history of allergy to therapeutic agents and compounds of similar composition;
• Contraindications to study drug or SIRT therapy, or to angiography as assessed by the Investigator;
• Pregnant or lactating women and those planning to conceive;
• Have participated in other research studies in the last 3 months;
• Inability to understand or unwillingness to sign a written informed consent form.

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

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 Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: February 24, 2025
• First Posted: March 10, 2025
• Study Start: March 1, 2025
• Primary Completion: March 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: March 10, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share