Trial Title:
Testing Immunotherapy for Patients With Liver Cancer and Moderately Altered Liver Functions
NCT ID:
NCT05622071
Condition:
Hepatocellular Carcinoma by BCLC Stage
Conditions: Official terms:
Carcinoma
Carcinoma, Hepatocellular
Tislelizumab
Conditions: Keywords:
Hepatocellular Carcinoma
tislelizumab
monotherapy
Child-Pugh B
ALBI grade 1 or 2 liver function score
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Multicentre, national, monotherapy, open-label, phase II single-arm study
Primary purpose:
Treatment
Masking:
None (Open Label)
Masking description:
Tislelizumab will be administered every 3 weeks IV for a maximum of 2 years
Intervention:
Intervention type:
Drug
Intervention name:
Tislelizumab
Description:
Tislelizumab 200 mg will be administered every 3 weeks IV for a maximum of 2 years
Arm group label:
SINGLE ARM
Other name:
BGB-A317
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.
Detailed 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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age ≥18 years old
2. Patient presenting with histologically-proven Hepatocellular Carcinoma (HCC), or HCC
defined by typical imaging findings (EASL criteria), if no biopsy could be performed
safely
3. Pretreated or not by tyrosine kinase inhibitors (e.g., sorafenib, lenvatinib,
regorafenib, cabozantinib)
4. Child-Pugh B cirrhosis
5. ALBI (Albumin-Bilirubin) grade 1 or 2
6. BCLC (Barcelona Clinic Liver Cancer Group) B or C
7. Availability of biopsy specimen at study enrolment (taken within 3 months of
enrolment with the exception of cases where biopsy could not be performed safely)
8. ECOG Performance status ≤2
9. Adequate organ function as indicated by the following laboratory values:
1. Patients must not have required a blood transfusion or growth factor support
≤14 days before sample collection at screening for the following:
- Absolute neutrophil count (ANC) ≥1.5 x 10⁹/L
- Platelets ≥75 x 10⁹/L
- Hemoglobin ≥90 g/L
2. Serum creatinine ≤1.5 x upper limit of normal (ULN) or estimated Glomerular
Filtration Rate ≥60 mL/min/1.73 m²
3. Serum total bilirubin ≤3 mg/dL
4. Liver function: ASAT and ALAT ≤5 ULN, albumin >2.0 g/dL
10. Presence of measurable and evaluable disease according to RECIST v1.1
11. Women of childbearing potential must be willing to use a highly effective method of
birth control for the duration of the study, and ≥120 days after the last dose of
tislelizumab, and have a negative urine or serum pregnancy test ≤7 days of first
dose of study drug. In case of a urine pregnancy test, it must be a highly sensitive
urine pregnancy test
12. Non-sterile males must be willing to use a highly effective method of birth control
for the duration of the study and for ≥120 days after the last dose of tislelizumab.
A sterile male is defined as one for whom azoospermia has been previously
demonstrated in a semen sample examination as definitive evidence of infertility.
Males with known "low sperm counts" (consistent with "sub-fertility") are not to be
considered sterile for purposes of this study
13. Patients must have provided consent for the study by signing and dating a written
informed consent form prior to any study specific procedures, sampling, or analyses.
When the patient is physically unable to give their written consent, a trusted
person of their choice, independent from the investigator or the sponsor, can
confirm in writing the patient's consent
14. Patient consent to the use of their collected tumour specimen, as well as blood
samples as detailed in the protocol for future scientific research which includes
but not limited to DNA, RNA, and proteinbased biomarker detection
15. Patient affiliated to a social security regimen
16. Men and women patients must consent to not donate or bank sperm or ova during
treatment and for 120 days after treatment stop
Exclusion Criteria:
1. More than 50% of the liver is affected by the HCC (according to investigators
evaluation)
2. Fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
3. Previous treatment with immunotherapy (anti-PD-1, anti-PD-L1, or anti-CTLA-4 agents)
4. History of active autoimmune disease. Note: Patients with the following diseases are
not excluded and may proceed to further screening:
1. Type I diabetes
2. Hypothyroidism (provided it is managed with hormone replacement therapy only)
3. Controlled celiac disease
4. Skin diseases not requiring systemic treatment (e.g., vitiligo, psoriasis,
alopecia)
5. Any other disease that is not expected to recur in the absence of external
triggering factors
5. History of interstitial lung disease, non-infectious pneumonitis or uncontrolled
diseases including pulmonary fibrosis, acute lung diseases
6. Any of the following cardiovascular risk factors:
1. Cardiac chest pain, defined as moderate pain that limits instrumental
activities of daily living, ≤28 days before first dose of study drug
2. Pulmonary embolism ≤28 days before first dose of study drug
3. Any history of acute myocardial infarction ≤6 months before first dose of study
drug
4. Any history of heart failure meeting New York Heart Association (NYHA)
Classification III or IV ≤6 months before first dose of study drug
5. Any event of ventricular arrhythmia ≥ Grade 2 in severity ≤6 months before
first dose of study drug
6. Any history of cerebrovascular accident ≤ 6 months before first dose of study
drug
7. Uncontrolled hypertension: systolic pressure ≥160 mmHg or diastolic pressure
≥100 mmHg despite anti-hypertension medications before first dose of drug
8. Any episode of syncope or seizure before first dose of study drug
7. Patients with untreated chronic hepatitis B or chronic hepatitis B virus (HBV)
carriers whose HBV DNA is >500 IU/mL or patients with active hepatitis C virus (HCV)
should be excluded. Note: Inactive hepatitis B surface antigen (HBsAg) carriers,
treated and stable hepatitis B (HBV DNA <500 IU/mL), and cured hepatitis C patients
can be enrolled
8. Known primary immunodeficiency or active HIV
9. Immunosuppression, including subjects with a condition requiring systemic treatment
with either corticosteroids (>10 mg/day prednisone equivalent) ≤14 days before
inclusion. Note: Patients who are currently or have previously been on any of the
following steroid regimens are not excluded:
1. Adrenal replacement steroid (dose ≤10 mg daily of prednisone or equivalent)
2. Topical, ocular, intra-articular, intranasal, or inhaled corticosteroid with
minimal systemic absorption
3. Short course (≤7 days) of corticosteroid prescribed prophylactically (e.g., for
contrast dye allergy) or for the treatment of a non-autoimmune condition (e.g.,
delayed-type hypersensitivity reaction caused by contact allergen)
10. Live vaccine within 4 weeks of first dose of study drug. Note: Seasonal vaccines for
influenza are generally inactivated vaccines and Covid vaccination with non-live
vaccine are allowed. Intranasal vaccines are live vaccines, and are not allowed
11. Transplanted liver, or patient with intent for transplantation
12. Received locoregional therapy to the liver (TACE, transcatheter embolization,
hepatic arterial infusion, radiation, radioembolization or ablation) in the 4 weeks
before inclusion
13. Prior malignancy active within the previous 3 years of inclusion except for locally
curable cancers considered cured or successfully resected, such as basal or squamous
cell skin cancers, superficial bladder cancer, or gastric cancers, or carcinoma in
situ of the prostate, cervix, or breast carcinomas. Any oncological concomitant
treatment are not allowed during the treatment period
14. Has received any herbal medicine used to control cancer with immunostimulant
properties that may interfere with liver function within 14 days of the first study
drug administration
15. Pregnant woman or breast-feeding women or patient with no adequate contraception
16. Participation in another therapeutic trial within the 30 days prior to study
inclusion
17. Patients deprived of their liberty or under protective custody or guardianship
18. Patients unable to adhere to the protocol for geographical, social, or psychological
reasons
19. Patients eligible for treatment by TACE or SIRT are not allowed
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
CHU Angers
Address:
City:
Angers
Country:
France
Status:
Recruiting
Contact:
Last name:
Frédéric Oberti
Facility:
Name:
Hôpital Avicenne
Address:
City:
Bobigny
Country:
France
Status:
Recruiting
Contact:
Last name:
Pierre Nahon, Prof
Facility:
Name:
CHU Beaujon
Address:
City:
Clichy
Country:
France
Status:
Recruiting
Contact:
Last name:
Mohamed Bouattour
Facility:
Name:
Hôpital Michallon
Address:
City:
Grenoble
Country:
France
Status:
Recruiting
Contact:
Last name:
Thomas Decaens, Prof
Facility:
Name:
CHU La Croix Rousse
Address:
City:
Lyon
Country:
France
Status:
Recruiting
Contact:
Last name:
Philippe Merle
Facility:
Name:
Hôpital Saint Joseph
Address:
City:
Marseille
Country:
France
Status:
Recruiting
Contact:
Last name:
Xavier Adhoute
Facility:
Name:
Institut Paoli Calmette
Address:
City:
Marseille
Country:
France
Status:
Recruiting
Contact:
Last name:
Simon Launay, Dr
Facility:
Name:
CHU Saint Eloi
Address:
City:
Montpellier
Country:
France
Status:
Recruiting
Contact:
Last name:
Eric Assenat
Facility:
Name:
Centre Eugene Marquis
Address:
City:
Rennes
Country:
France
Status:
Recruiting
Contact:
Last name:
JULIEN EDELINE, PH
Facility:
Name:
CHRU Strasbourg
Address:
City:
Strasbourg
Country:
France
Status:
Recruiting
Contact:
Last name:
Antonio Saviano, Dr
Start date:
October 12, 2023
Completion date:
April 4, 2028
Lead sponsor:
Agency:
UNICANCER
Agency class:
Other
Source:
UNICANCER
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05622071
