A Multicenter Clinical Study of Combined Therapy for Unresectable Hepatocellular Carcinoma

March 15, 2026 updated by: LiuChang, West China Hospital

A Multicenter Phase Ib/II Clinical Study on the Safety and Efficacy of Selective Internal Radiation Therapy (SIRT) With Yttrium-90 Microspheres in Combination With Nivolumab, Ipilimumab, and Lenvatinib in Patients With Unresectable Hepatocellular Carcinoma

This clinical trial was designed to evaluate the safety and efficacy of Y90-SIRT combined with nivolumab, ipilimumab, and lenvatinib in patients with unresectable HCC. In addition to assessing short-term efficacy endpoints, such as ORR and PFS, this trial places particular emphasis on the OS benefit for patients. This study is therefore both novel and innovative.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

33

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Sichuan
      • Chengdu, Sichuan, China, 610041
        • Recruiting
        • Study Chair Liu Chang , West China Hospital
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. HCC confirmed as unresectable by imaging or histology, or patients who refuse surgery. Eligible for Y90-SIRT, with no evidence of extrahepatic disease on any available imaging. Lymph node involvement is permitted. The term "unresectable hepatocellular carcinoma" refers to a clinical state in which radical surgical resection is precluded because the tumor extent or an inadequate anticipated future liver remnant would prevent R0 removal, or because the procedural risk is prohibitively high, and where surgical intervention is not expected to yield a survival advantage over non-surgical therapies.
  2. Aged between 18 and 80 years at the time of enrollment
  3. Participants with Child-Pugh class A.
  4. Participants with an ECOG performance status of 0 or 1 at the time of enrollment
  5. Participants with a lung dose threshold of 30 Gy for yttrium-90 microspheres (each treatment dose ≤ 30 Gy), and an anticipated future liver remnant volume (FLRV) ≥ 30% of the total liver volume.
  6. Participants with one or more measurable lesions; for those with segmental or right anterior/posterior portal vein invasion (Vp1/Vp2), the disease is confined to a single lobe and suitable for Y90 microsphere treatment.
  7. If the patient is co-infected with hepatitis B virus (HBV) or hepatitis C virus (HCV), the following criteria must be met: HBV or HCV viral levels should be monitored during study participation. Patients with detectable hepatitis B surface antigen (HBsAg) or HBV DNA should have HBV DNA < 100 IU/ml and be managed according to local treatment guidelines. Most patients with advanced HCC and HCV have not received treatment for HCV infection. However, if antiviral therapy has been completed prior to the first administration of study drugs, these patients are considered eligible for inclusion.
  8. No prior systemic therapy or transarterial radioembolization (Y90 glass microsphere TARE).
  9. No active autoimmune disease and no history of chronic or recurrent autoimmune disease.
  10. Adequate hematological, liver, and renal function as follows: (1) Absolute neutrophil count ≥ 1,500/mm³ (2) Hemoglobin level ≥ 9.0 g/dL (3) Platelet count ≥ 75,000/mm³ (4) Total bilirubin ≤ 1.5 × ULN (5) AST ≤ 2.5 × ULN (6) ALT ≤ 2.5 × ULN (7) International normalized ratio (INR) ≤ 1.25 (8) Albumin ≥ 31 g/L (9) 24-hour urine collection creatinine clearance (CL) > 40 mL/min or calculated creatinine clearance (CL) > 40 mL/min.
  11. Not pregnant and no intention to conceive before or during treatment.
  12. Written informed consent from the patient.
  13. Expected survival of at least 12 weeks.

Exclusion Criteria:

  1. Diffuse HCC or presence of vascular invasion or extrahepatic spread, with the following exceptions: invasion of segmental portal vein or hepatic vein.
  2. Patients with Child-Pugh class C cirrhosis.
  3. Any contraindication to hepatic arterial embolization: Known hepatic arterial reflux; known portosystemic shunt; coagulopathy (platelet count < 50 × 109/L, INR > 1.5); renal failure/insufficiency requiring hemodialysis or peritoneal dialysis; known severe arteriosclerosis; complete thrombosis or complete invasion of the main portal vein.
  4. History of heart disease: congestive heart failure > New York Heart Association (NYHA) class II; active coronary artery disease (CAD) (myocardial infarction ≥ 6 months prior to study initiation is permitted); arrhythmias that are difficult to control with antiarrhythmic drugs or require a pacemaker (NCI-CTCAE v5.0 > grade 2); uncontrolled hypertension; clinically significant gastrointestinal bleeding within 4 weeks prior to initiation of study drugs.
  5. Thrombotic or embolic events, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis, or pulmonary embolism, occurring within 6 months prior to the first administration of study drug, except for segmental portal vein thrombosis.
  6. Receipt of systemic anticancer therapy, radiotherapy, endocrine therapy, immunotherapy, or other investigational drugs within 4 weeks prior to study initiation.
  7. Current or prior use of immunosuppressive drugs within 28 days before the first administration of nivolumab or ipilimumab. Exceptions to this criterion include: intranasal, inhaled, topical steroids or local steroid injections (e.g., intra-articular injection); physiological doses of systemic corticosteroids not exceeding 10 mg/day of prednisone or equivalent; steroids used for the prevention of allergic reactions (e.g., premedication for CT scan).
  8. Receipt of live attenuated vaccines within 30 days prior to the first administration of study drug (IP). Note: If the patient is enrolled, live vaccines should not be administered during the study drug treatment period and within 30 days after the last dose of the study drug.
  9. Major surgery within 4 weeks prior to study initiation, and the patient must have recovered from the effects of major surgery.
  10. Patients with a second primary malignancy, apart from adequately treated basal cell carcinoma of the skin or carcinoma in situ of the cervix, unless disease-free for more than 3 years.
  11. Uncontrolled comorbidities, including but not limited to persistent or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina, arrhythmia, interstitial lung disease, severe chronic gastrointestinal disease associated with diarrhea, or psychiatric/social conditions that limit compliance with study requirements, significantly increase the risk of adverse events, or impair the patient's ability to provide written informed consent.
  12. Active infections, including tuberculosis (clinical assessment including medical history, physical examination, and imaging, as well as tuberculosis testing according to local practice), hepatitis B (known positive HBV surface antigen [HBsAg]), and hepatitis C. Patients with past or resolved HBV infection (defined as presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients who are HCV antibody-positive are eligible only if HCV RNA measured by PCR is negative.
  13. History of allogeneic organ transplantation.
  14. Psychiatric disorders or altered mental status that interfere with understanding the informed consent process and/or compliance with the study protocol.
  15. Symptomatic brain metastases. If symptoms are present, imaging is required to confirm the absence of brain metastases.
  16. Pregnant or breastfeeding women.
  17. Immunocompromised patients, such as those known to be serologically positive for human immunodeficiency virus (HIV).
  18. Active or previously documented autoimmune or inflammatory diseases (including inflammatory bowel disease [such as colitis or Crohn's disease], diverticulitis [excluding diverticulosis], systemic lupus erythematosus, sarcoidosis, or Wegener's granulomatosis [granulomatosis with polyangiitis], Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, among others).
  19. Known allergy or hypersensitivity to any study drug or its components.
  20. Currently participating in or previously participated in a study involving an investigational drug, or use of an investigational device within 4 weeks prior to the first administration of study treatment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Yttrium-90 microspheres in combination with nivolumab, ipilimumab, and lenvatinib
The phase Ib portion of the trial explores the incidence of dose-limiting toxicity (DLT) in the quadruple therapeutic regimen. Three weeks after receiving Y90-SIRT, the patients are assigned to one of three dose exploration cohorts: (1) nivolumab 1 mg/kg IV every 3 weeks (Q3W) + ipilimumab 1 mg/kg IV Q3W for up to 4 cycles; (2) nivolumab 1 mg/kg IV Q3W + ipilimumab 2 mg/kg IV Q3W for up to 4 cycles; (3) nivolumab 1 mg/kg IV Q3W + ipilimumab 3 mg/kg IV Q3W for up to 4 cycles. After completion of ipilimumab administration, nivolumab is continued at 480 mg IV every 4 weeks (Q4W) until disease progression, unacceptable toxicity, withdrawal of informed consent, or a maximum treatment duration of two years. Lenvatinib is then administered after discontinuation of ipilimumab, in combination with nivolumab, at a dose of 8 mg (body weight <60 kg) or 12 mg (body weight >60 kg) orally once daily (PO QD), taken at a fixed time each day, with or without food.
Drug: ttrium-90 microspheres in combination with nivolumab, ipilimumab, and lenvatinib in patients with unresectable hepatocellular carcinoma
The phase Ib portion of the trial explores the incidence of dose-limiting toxicity (DLT) in the quadruple therapeutic regimen. Three weeks after receiving Y90-SIRT, the patients are assigned to one of three dose exploration cohorts: (1) nivolumab 1 mg/kg IV every 3 weeks (Q3W) + ipilimumab 1 mg/kg IV Q3W for up to 4 cycles; (2) nivolumab 1 mg/kg IV Q3W + ipilimumab 2 mg/kg IV Q3W for up to 4 cycles; (3) nivolumab 1 mg/kg IV Q3W + ipilimumab 3 mg/kg IV Q3W for up to 4 cycles. After completion of ipilimumab administration, nivolumab is continued at 480 mg IV every 4 weeks (Q4W) until disease progression, unacceptable toxicity, withdrawal of informed consent, or a maximum treatment duration of two years. Lenvatinib is then administered after discontinuation of ipilimumab, in combination with nivolumab, at a dose of 8 mg (body weight <60 kg) or 12 mg (body weight >60 kg) orally once daily (PO QD), taken at a fixed time each day, with or without food.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of dose-limiting toxicity (DLT) of the quadruple regimen (Y90-SIRT plus nivolumab, ipilimumab, lenvatinib)
Time Frame: Up to 4 treatment cycles (each cycle is 3 weeks)
Up to 4 treatment cycles (each cycle is 3 weeks)
Objective response rate (ORR) assessed by both iRECIST and mRECIST criteria
Time Frame: 24 months
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

West China Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

February 1, 2026

Primary Completion (Estimated)

June 30, 2026

Study Completion (Estimated)

June 30, 2028

Study Registration Dates

First Submitted

February 27, 2026

First Submitted That Met QC Criteria

March 15, 2026

First Posted (Actual)

March 19, 2026

Study Record Updates

Last Update Posted (Actual)

March 19, 2026

Last Update Submitted That Met QC Criteria

March 15, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20252727

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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