EOADUVANT ATEZOLIZUMAB AND ADJUVANT ATEZOLIZUMAB + BEVACIZUMAB IN COMBINATION WITH PERCUTANEOUS RADIOFREQUENCY ABLATION OF SMALL HCC

Phase 1

• Conditions: Digestive oncology; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2020-000569-18-FR
• Lead Sponsor: niversity Hospital of Montpellier

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-09-08
• Last Update Posted: 19 October 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 202

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 <3cm
- 1-3 nodules of HCC
•At least one uni-dimensional measurable lesion by magnetic resonance imaging (MRI) according to modified RECIST criteria
•Liver function status Child-Pugh Class A
•Eastern Cooperative Oncology Group (ECOG) Performance Status = 1
•Adequate bone marrow, liver and renal function as assessed by the following laboratory tests:
- Hemoglobin > 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

- 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 (<5mm) is allowed. Calcified lung micronodules as well as typical intra-pulmonary lymph nodes are allowed. Hepatic hilum lymph node < 10mm (short axis) is allowed.
- Prior surgery of HCC with micro- or macro-vascular invasion demonstrated at pathology.
- Prior systemic treatment for HCC, in particular agents targeting T-cell costimulation or checkpoint pathways (including those targeting PD-1, PD-L1 or PD-L2, CD137, or cytotoxic T-lymphocyte antigen [CTLA-4]).
- Patients with uncontrolled HBV infection and viral load above 500 IU/mL.
- Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high risk for bleeding. Patients must undergo an esophagogastroduodenoscopy (EGD), and all size of varices (small to large) must be assessed and treated per local standard of care prior to enrollment. Patients who have undergone an EGD within 6 months of prior to initiation of study treatment do not need to repeat the procedure
- Past or concurrent history of neoplasm other than HCC, except for in-situ carcinoma of the cervix uteri and/or non-melanoma skin cancer and superficial bladder tumors. Any cancer curatively treated > 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)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified