Testing Immunotherapy for Patients With Liver Cancer and Moderately Altered Liver Functions — HESTIA  

Hepatocellular Carcinoma by BCLC Stage Clinical Trial

Official title: A Multicentric National Phase II Trial Assessing TIslelizumab in Monotherapy for Patients With Hepatocellular Carcinoma Child-Pugh B and ALBI Grade 1 or 2 Liver Function Score

Status Recruiting

Clinical Trial Summary

Liver cancer is the third leading cause of cancer-related deaths worldwide. The majority of primary liver cancers occur as hepatocellular carcinoma (HCC), the incidence of which is increasing in many parts of the world. The vast majority of HCC cases occur in the setting of liver cirrhosis, usually due to chronic viral infections with hepatitis C or hepatitis B, alcohol consumption, non-alcoholic fatty liver disease or diabetes. The degree of underlying liver disease, as well as the stage of the tumour and the general condition of the patients, should therefore be taken into account when deciding on the treatment of HCC. Most patients with HCC have advanced disease at the time of diagnosis, or have recurrent disease after potentially curative treatments.

Tislelizumab showed enhanced cellular functional activities by blocking PD-1-mediated reverse signal transduction and activating human T cells and primary peripheral blood mononuclear cells in vitro.

Based on this preliminary safety profile, and knowing that there is antitumour activity, we can offer tislelizumab as a single agent in patients with unresectable HCC.

HESTIA study is a multicentric French national phase II trial assessing tislelizumab in monotherapy for patients with Hepatocellular Carcinoma Child-Pugh B and ALBI grade 1 or 2 liver function score.

It is planned to include 50 patients in the study. All patients will be recruited in France. The study will be presented to eligible patients at participating centres and an information note will be provided. No advertising material is planned for this study.

To be eligible, patients must meet all the following criteria to be ≥18 years old, with histologically proven Hepatocellular Carcinoma (HCC), pre-treated or not with a tyrosine kinase inhibitor and Child-Pugh B cirrhosis, ALBI (Albumin-Bilirubin) grade 1 or 2 and BCLC (Barcelona Clinic Liver Cancer Group) B or C and with no more than 50% liver invasion of tumour disease.

Clinical Trial Description

The primary objective is to assess efficacy of anti-PD1 (in terms of Objective Response Rate [ORR] based on Best Overall Response across all time-points as defined by RECIST v1.1) in the Child-Pugh B / ALBI grade 1/2 population.

Secondary objectives are :

• To assess safety of anti-PD-1

• To assess efficacy in terms of:

• Objective Response Rate based on best overall response across all time-point according to mRECIST and iRECIST tumor response evaluation

• Overall survival (OS)

• Progression-free survival (PFS)

• Time to progression (TTP)

• To assess Quality of Life according to EORTC QLQ-C30 and HCC-18.

In order to confirm the eligibility of patients, a clinical examination, biological blood tests, ECG, CT scan and a urine or blood pregnancy test for women of childbearing age will be performed. A quality of life questionnaire will be administered to patients. Patients will also be asked to agree to a full eye examination by an ophthalmologist prior to the start of treatment to determine that there is no risk of worsening the patient's visual acuity with treatment with tislelizumab.

After enrolment in the study, the patient will be required to visit the hospital every 3 weeks to receive intravenous treatment for up to 2 years.

Once the treatment is completed, the patient will be seen at follow-up visits for 2 years, initially every 3 months for the first year and then every 6 months for the second year.

Assessment of tumour response by CT or MRI will be done after the start of treatment at weeks 9, 18, 27, 54 and every 12 weeks until disease progression and throughout the treatment period. Tumour assessment by CT or MRI will be performed 2 years after the start of treatment or upon disease progression.

Patients will be asked to consent to the use of a collected tumour sample, as well as to the collection of blood samples, for future scientific research which includes, but is not limited to, the detection of DNA, RNA and protein biomarkers.

An independent Study Monitoring Board (DSMB), with expertise and experience in the pathology, and without direct involvement in the conduct of the study, will be set up specifically to ensure optimal safety monitoring during the early phase of the study and the feasibility of at least 2 treatment injections (6 weeks from inclusion), an early stopping rule has been defined for the first 20 patients included. This method was chosen for the evaluation of serious adverse events (SAEs), which may occur relatively early in this trial. A high frequency of occurrence may necessitate early termination of the trial. ;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma by BCLC Stage

• NCT number: NCT05622071
• Study type: Interventional
• Source: UNICANCER
• Contact: Veronica Pezzella
• Phone: + 33 (0)1 44 23 04 04
• Email: v-pezzella@unicancer.fr
• Status: Recruiting
• Phase: Phase 2
• Start date: October 12, 2023
• Completion date: April 4, 2028