Improving the Use of Immunotherapy to Treat Liver Cancer

Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversitaire Ziekenhuizen KU Leuven

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

General

Male or female, age > 18 years

Diagnosis or suspected diagnosis of hepatocellular carcinoma based on imaging

Pathologically confirmed HCC

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • Blood and tissue sample

    Other intervention

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

Treatment groups

300 Participants
are divided into 3 treatment groups
Group A: Cohort 1No intervention 0 interventions
Group B: Cohort 2Other 1 intervention
Group C: Cohort 3Other 1 intervention

Trial outcomes

Primary outcomes

1

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.

Time frame
Through study completion, an average of 6 months
2

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.

Time frame
Through study completion, an average of 6 months
3

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).

Time frame
Through study completion, an average of 6 months
4

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).

Time frame
12 months after tissue acquisition

Secondary outcomes

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Universitaire Ziekenhuizen KU Leuven

Lead sponsor

Flemish institute of biotechnology (VIB)

Collaborator