Improving the Use of Immunotherapy to Treat Liver Cancer

NCT07623265 | Recruiting

• 1 other identifier: S69815
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 4

Brief Summary

This project targets patients with a form of primary liver cancer, specifically "hepatocellular carcinoma". This disease often develops in the context of a chronically diseased liver, caused by viral infections, excessive alcohol consumption, or fatty liver. Primarily due to the rise of the latter risk factor, liver cancer is one of the few cancer types whose incidence continues to increase globally, year after year. As a result, liver cancer has become the third most common cause of cancer-related deaths worldwide. There exists a significant challenge in reducing the disease on all fronts: prevention, diagnosis, and treatment. This research aims to personalize the treatment of liver cancer patients, tailoring it to the individual. More specifically, this research seeks to identify patients with immunotherapy-sensitive liver cancer by biomarkers before treatment begins. Determining whether a tumor is immunotherapy-sensitive is internationally recognized as one of the most important challenges within this condition. Based on a combination of existing laboratory techniques on tumor tissue and/or blood, the investigators seek to predict the likelihood of this treatment's success before initiating it. With this knowledge, the investigators could recommend alternative treatments to patients with tumors that are unresponsive. This way, they would also avoid exposure to the side effects of an ineffective therapy.

Conditions

Hepatocellular Carcinoma (HCC)

Keywords

Biomarker; Hepatocellular carcinoma; Immunotherapy

Outcome Measures

Primary Outcomes (4)

• Spatial orientation

  Spatial orientation of cell types of interest in the tumour microenvironment (TME) of HCC using a variety of techniques: multiplex IHC, spatial proteomics and spatial transcriptomics. Samples from early (cohort 3) and advanced HCC (cohort 2) will be used.

  Through study completion, an average of 6 months

• TCR sharing

  Identification of shared TCR sequences between PBMCs and tumor tissue using RNA and TCR sequencing. Exploration of the degree of TCR sharing in early and advanced HCC.

  Through study completion, an average of 6 months

• Antigen identification

  The investigators will use tumor tissue and PBMC to construct an antigenic landscape of advanced HCC. To achieve this goal the investigators will use a unique technique called Transcriptome-Wide Screening for T cell Antigen Research (TWISTAR).

  Through study completion, an average of 6 months

• Biomarker validation

  This study will be used to validate two candidate predictive biomarkers (CD45RA effector-memory CD8 T-cells/PDL1-expressing CXCL10+ macrophages) AND TCR sharing between tumor and blood in relation to response to immunotherapy in HCC. The investigators will compare the biomarker positive and biomarker negative groups in terms of progression-free survival and overall survival (Kaplan-Meier time-to-event) in the context of known prognostic clinical variables (multivariable cox proportional hazards model).

  12 months after tissue acquisition

Study Arms (3)

Cohort 1

NO INTERVENTION

Cohort 1 (observational): * Collection of leftover archival tumour tissue of patients with advanced HCC treated with systemic therapies. * No blood collection. * Retrospective and prospective collection of data.

Cohort 2

OTHER

Cohort 2 (advanced HCC): * Prospective collection of tumour tissue at the time of standard of care biopsy from advanced HCC patients prior to initiation of a systemic treatment (max 2 needle biopsy cylinders). * Additional collection of leftover archival tissue from previous biopsies or resection specimens is possible. * Prospective collection of blood samples at two timepoints (prior to start of systemic treatment and prior to the 2nd therapy cycle). Maximum 30ml of blood per timepoint (3x10ml EDTA tubes). * Retrospective and prospective collection of data.

Other: Blood and tissue sample

Cohort 3

OTHER

* Prospective collection of tumour tissue at the time of standard of care biopsy (max 2 needle biopsy cylinders) or surgical treatment (resection or ablation; 2 surgical biopsies or a piece of the resection specimen) from early HCC patients. * Additional collection of leftover archival tissue from previous biopsies or resection specimens is possible. * Prospective collection of blood samples at one timepoint (prior to resection or ablation). Maximum 30ml of blood per timepoint (3x10ml EDTA tubes). * Retrospective and prospective collection of data.

Other: Blood and tissue sample

Interventions

Blood and tissue sample OTHER

Prospective collection of additional blood and tissue samples for study-specific analyses at specific timepoints, at the same time as routine procedures.

Cohort 2; Cohort 3

Eligibility Criteria

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

You may qualify if:

• Male or female, age \> 18 years
• Diagnosis or suspected diagnosis of hepatocellular carcinoma based on imaging
• Pathologically confirmed HCC
• Treated with systemic treatment \[tyrosine kinase inhibitor (TKI) or immunotherapy (ICI)\] in the last 7 years and follow-up data (at least one imaging on treatment) available until 01/01/2025
• Biopsy obtained between 01/01/2018 until 01/01/2025
• Left-over tissue from previous diagnostic biopsies or resection specimens available
• Time between biopsy and initiation of systemic treatment \< 1 year
• Ability to sign informed consent for secondary use of archival tissue and data collection for study-specific research for patients who are alive
• Suspicion of hepatocellular carcinoma (imaging criteria or recurrent disease of previously treated HCC)
• Indication for tumor biopsy per standard of care
• Eligible for systemic treatment (any) after pathological confirmation of HCC
• Ability to sign informed consent for primary use of tissue and blood samples and data collection for study-specific research
• Suspicion of hepatocellular carcinoma (imaging criteria or recurrent disease of previously treated HCC)
• Indication for local treatment (resection or ablation)
• Ability to sign informed consent for primary use of tissue and blood samples and for data collection for study-specific research

You may not qualify if:

• Poor liver function and/or performance status which prohibits active treatment
• Pathologically proven other malignancies of the liver, including primary cholangiocarcinoma or liver metastases
• Treatment plan other than systemic treatment or local treatment (resection or ablation), such as TACE, TARE, liver transplantation

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead
• Flemish institute of biotechnology (VIB): collaborator

Study Sites (4)

UZA

Antwerp, Belgium

RECRUITING

Jessa ziekenhuis

Hasselt, Belgium

RECRUITING

AZ Groeninge

Kortrijk, Belgium

RECRUITING

AZ Delta

Roeselare, Belgium

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Blood Specimen Collection; Histocompatibility Testing

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)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Immunologic Tests; Immunologic Techniques

Central Study Contacts

Jeroen Dekervel, MD

CONTACT

016344225; jeroen.dekervel@uzleuven.be

Frederik Peeters, MD

CONTACT

frederik.1.peeters@uzleuven.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Three patient cohorts are defined, depending on the therapeutic scenario patients undertake. Patient management is standard of care. No investigational medicinal product (IMP) is involved. Trial is considered low interventional due to addition of extra blood and tissue samples, otherwise would be observational.

Study Record Dates

• First Submitted: February 6, 2025
• First Posted: June 3, 2026
• Study Start: March 4, 2025
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2032
• Last Updated: June 3, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

BE (4)