Partial Immune-boost TACE in unrEseCTable HCC Patients Under Systemic Treatment

Not Applicable

Not yet recruiting

• Conditions: HCC; Tace; Immunotherapy
• Interventions: Procedure: Transarterial chemoembolization; Drug: durvalumab and tremelimumab

• Registration Number: NCT07168668
• Lead Sponsor: Chang Gung Memorial Hospital

Brief Summary

Study Objectives： Atezolizumab (anti-programmed death-ligand 1; anti-PD-L1) combined with bevacizumab (anti-vascular endothelial growth factor; anti-VEGF) or Durvalumab (anti-programmed death-ligand 1; anti-PD-L1) combined with tremelimumab (anti-cytotoxic T-lymphocyte-associated protein 4; anti-CTLA4) have recently been established as a standard first-line systemic treatment for unresectable hepatocellular carcinoma (HCC). However, its objective response rate (ORR) is only less than 27% (1, 2), and the majority of patients died of HCC progression and liver failure. Therefore, there is an urgent need to develop a novel combination treatment strategy to overcome resistance to immunotherapy and improve patient outcomes.

Transarterial chemoembolization (TACE) remains the standard treatment for patients with intermediate-stage hepatocellular carcinoma (HCC) (3, 4). However, in our previous retrospective study (5-7), the investigators consistently observed that this combination not only improves therapeutic responses but also significantly prolongs patient survival. The tumor necrosis caused by TACE may enhance the efficacy of systemic therapies by promoting the release of neoantigens, thereby stimulating immune responses (8-14). This concept has been substantiated in two recent trials involving intermediate-stage HCC (15, 16), where the addition of immune checkpoint inhibitors to TACE resulted in improved clinical outcomes. Nevertheless, this promising approach has yet to replace the decades-old standard treatment protocols, underscoring the need for further proof-of-concept studies.

Both immunotherapy (atezolizumab/bevacizumab or durvalumab/tremelimumab) and transarterial chemoembolization (TACE) are approved treatment modalities for unresectable hepatocellular carcinoma (HCC) by the U.S. and Taiwan Food and Drug Administration (FDA). This phase II non-randomized trial is designed to prospectively evaluate the therapeutic efficacy, safety, and immunological responses in patients with unresectable HCC treated with a combination of immunotherapy and TACE. A particular focus of this study is to explore the potential immune-boosting effects of TACE, including its ability to enhance antigen presentation and stimulate anti-tumor immune responses.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-08
• Study First Submitted: 2025-09-03
• Study First Submitted QC: 2025-09-04
• Last Update Submitted: 2025-09-04
• Study First Posted: 2025-09-11
• Last Update Posted: 2025-09-11
• Study Start: 2025-09-15
• Primary Completion: 2028-05-30
• Study Completion: 2028-05-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

Not provided

Exclusion Criteria

1. Prior invasive malignancy unless disease free for a minimum of 2 years

2. Prior radiotherapy to the region of the liver that would result in overlap of embolization fields

3. Prior selective internal radiotherapy/hepatic arterial yttrium therapy, at any time

4. Untreated active hepatitis B or hepatitis C

5. Moderate to severe or intractable ascites

6. Untreated or incomplete treated esophageal or gastric varices

7. Severe, active co-morbidity, defined as follows:

   • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months prior to registration
   • Myocardial infarction within the last 6 months prior to study entry
   • Acute bacterial or fungal infection requiring intravenous antibiotics within 28 days prior to study entry
   • A bleeding episode within 6 months prior to study entry due to any cause. o Thrombolytic therapy within 28 days prior to study entry.
   • Known bleeding or clotting disorder.
   • Uncontrolled psychotic disorder

8. Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception

9. Prior solid organ transplantation.

10. Prior or active autoimmune disease (AID) including autoimmune hepatitis, inflammatory bowel disease, myasthenia gravis, systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, and multiple sclerosis.

11. Prior or active thrombotic or bleeding disorders, hemoptysis, cerebral vascular accident, significant cardiac disease (ischemic or congestive heart failure), or gastrointestinal perforation.

12. Known HIV infection.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
partial TACE with systemic treatment	Transarterial chemoembolization	partial TACE
partial TACE with systemic treatment	durvalumab and tremelimumab	partial TACE

Primary Outcome Measures

Name	Time	Method
PFS	From enrollment to the end of treatment at 12 months	PFS 12 month

Secondary Outcome Measures

Name	Time	Method
ORR	12 months	Best ORR
OS	OS 3 years	OS 3 years
DOR	Up to 3 years	Duration of response
The function of innate CD8+ T cells	Up to 3 years	Evaluate innate-like CD8⁺ T-cell function using participants' peripheral blood mononuclear cells (PBMCs).