Digestive oncology
Conditions
Sponsors
University Hospital of Montpellier
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Male or female patients = 18 years of age •Diagnostic of HCC based on histology Patients with HCC eligible for ablation as assessed by multidisciplinary board: - All HCC nodules 8.5 g/dL - Absolute neutrophil count = 1500/mm3 - Platelet count = 50,000/ mm3 - Total bilirubin = 2 mg/dL - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 5 x upper limit of normal (ULN) - Serum creatinine = 1.5 x ULN - Lipase = 2 x ULN - Prothrombin time > 50% - Glomerular Filtration Rate (GFR) = 35 mL/min/1.73 m2 •Life expectancy = 3 months •Women of childbearing potential and men must agree to use adequate contraception during the study and for 5 months after stopping Treatment •Patients affiliated to a Social Security System Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 182 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: - Patients with contraindications to ablation or atezolizumab or bevacizumab - Patients with contraindication to contrast medium intravenous injection either gadolinium or iodinate - Patients with contraindication to MRI - Prior liver transplantation or candidates for liver transplantation - Child-Pugh B or C - Patients with mixed histology (HCC and cholangiocarcinoma, namely hepatocholangiocarcinoma) - Treatment with anticoagulants (heparin or AVK) that cannot be interrupted for 48 hours - Treatment with anti-platelets (especially aspirin, Plavix®) that cannot be interrupted for 5 days. - Portal vein invasion, whatever its extent, shown on baseline imaging - Prior chemoembolization or radioembolization. - Patients with extra-hepatic metastases, either previously-treated or not. One lung nodule ( 3 years prior to study entry is permitted - Known history or symptomatic meningeal tumors - Grade 3 (severe) hypertension =160 and/or =100 mmHG (systolic and diastolic, according to NCI-CTCAE v5.0) - Patients with phaeochromocytoma - Ongoing infection. Hepatitis B is allowed if no active replication is present (HBV replication below 500 IU/mL). Hepatitis C is allowed if no antiviral treatment is required - Clinically significant bleeding NCI-CTCAE version 5.0 = Grade 3 within 30 days before enrolment (transfusion indicated) - Arterial or venous thrombotic or embolic events such as cerebrovascular accident, deep vein thrombosis or pulmonary embolism within 6 months before enrolment - Any psychological, familial, sociological, geographical or illness or medical condition that could jeopardize the safety of the patient and/or his compliance with the study protocol and follow-up procedure - Known history of human immunodeficiency virus (HIV) infection - Seizure disorder requiring medication - Non-healing wound, ulcer or bone fracture - Breast feeding - Pregnancy - Legal incapacity (persons in custody or under guardianship) - Deprived of liberty Subject (by judicial or administrative decision)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective is to compare RFS (recurrence-free survival) at 2-years (by the investigator) after the radiofrequency ablation procedure.;Secondary Objective: The secondary objectives are: •To compare RFS at 2 years according to independent central review •To evaluate the compliance to neoadjuvant and adjuvant treatments •To evaluate the tolerance of atezolizumab in the setting of neo-adjuvant therapy to ablation, and atezolizumab + bevacizumab in the setting of adjuvant therapy to ablation •To compare health-related quality of life (HRQoL) in experimental arm vs. control arm •To compare incidences of local-, intrahepatic- and extrahepatic recurrence in experimental arm vs. control arm •To compare time-to-recurrence in experimental arm vs. control arm •To compare overall survival in experimental arm vs. control arm •To compare OS rate at 3 and 5 years after the radiofrequency ablation procedure. •Translational research (please find details further) ;Primary end point(s): Recurrence-free survival: Recurrence is defined as recurrence or death, whichever comes first Recurrence is defined as emergence of = 1cm nodules enhanced at arterial phase followed by washout at portal or late phase observed on MRI, or any atypical nodule on imaging with histological features of HCC (EASL guidelines). Emergence of extrahepatic metastasis is also considered as a recurrence. ;Timepoint(s) of evaluation of this end point: Patients will be followed by MRI, 3 months, 6 months, 9 months, 12 months, 18 months and 24 months after randomization according to French guidelines; Chest CT-scan every 6 months . For the main endpoint, recurrence is evaluated by the local investigator. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Recurrence-free survival as evaluated by independent central review - Compliance (number of patients taking the full dose of atezo/beva up to 1 year after ablation; mean treatment duration per patient; number of treatment discontinuation together with reasons for discontinuation). - Tolerance - HRQoL assessed by the EORTC QLQ-C30 (GHS/Qol, physical function, role function, appetite loss, diarrhea, fatigue, pain) and its module QLQ-HCC18 (fatigue, jaundice, pain) - Time-to-recurrence (estimated by the time between the date of randomization and the date of recurrence as shown on according to the investigator's opinion) - Overall survival (estimated by the time between the date of randomization and the date of death or date of last news for alive patients) ;Timepoint(s) of evaluation of this end point: at baseline, RFA, and during the follow-up: month 3, 6, 9, 12, 18 and 24 after randomization | — |
Countries
France
Contacts
Public ContactSandrine MAS
University hospital of Montpellier
Outcome results
None listed