Bevacizumab for Hepatocellular carcinoma

Inclusion criteria

• {"criterion_text":"- •\tMale or female patients ≥ 18 years of age\n- •\tDiagnosis of HCC based on imaging (EASL guidelines)\n- •\tPatients with HCC eligible for ablation as assessed by multidisciplinary board: o\tAll HCC nodules ≤ 3cm o\t1-3 nodules of HCC\n- •\tAt least one uni-dimensional measurable lesion by magnetic resonance imaging (MRI) according to modified RECIST criteria\n- •\tLiver function status Child-Pugh Class A\n- •\tEastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1\n- •\tAdequate bone marrow, liver and renal function as assessed by the following laboratory tests: o\tHemoglobin > 8.5 g/dL o\tAbsolute neutrophil count ≥ 1500/mm3 o\tPlatelet count ≥ 50,000/mm3 o\tTotal bilirubin ≤ 2 mg/dL (or ≤ 34 mol/L). o\tAlanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x upper limit of normal (ULN) o\tSerum creatinine ≤ 1.5 x ULN o\tLipase ≤ 2 x ULN o\tProthrombin time > 50% o\tGlomerular Filtration Rate (GFR) ≥ 35 mL/min/1.73 m2\n- •\tLife expectancy ≥ 3 months\n- •\tWomen of childbearing potential and men must agree to use adequate contraception\n- •\tPatients affiliated to a Social Security System"}

Exclusion criteria

• {"criterion_text":"- •\tPatients with contraindications to ablation or atezolizumab or bevacizumab\n- •\tPatients with contraindication to contrast medium intravenous injection either gadolinium or iodinate\n- •\tPatients with contraindication to MRI\n- •\tPrior liver transplantation\n- •\tChild-Pugh B or C\n- •\tPatients with mixed histology (HCC and cholangiocarcinoma, namely hepatocholangiocarcinoma), if a biopsy is available.\n- •\tCurrent or recent (≤ 10 days prior to initiation of study treatment) use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic) purpose. Prophylactic anticoagulation for the patency of venous access devices is allowed provided the activity of the agent results in an INR < 1.5 x ULN and aPTT is within normal limits within 14 days prior to initiation of study treatment.NB: all anticoagulation treatments, provided they are used as prophylaxis, are allowed.\n- •\tCurrent or recent (≤ 10 days prior to initiation of study treatment) use of aspirin (> 325 mg/day) or treatment with clopidogrel, dipyramidole, ticlopidine, or cilostazol.\n- •\tActive or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:\n- a.\tPatients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.\n- b.\tPatients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.\n- c.\tPatients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g. patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:\n- – Rash must cover < 10% of body surface area.\n- – Disease is well controlled at baseline and requires only low-potency topical corticosteroids.\n- – No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids.\n- •\tTreatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-α agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions:\n- – Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g. 48 hours of corticosteroids for a contrast allergy) are eligible for the study after Medical Monitor confirmation has been obtained.\n- – Patients who received mineralocorticoids (e.g. fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligiblefor the study.\n- •\tPortal vein invasion, whatever its extent, shown on baseline imaging\n- •\tPrior liver arterial embolization, chemoembolization or radioembolization.\n- •\tPatients with extra-hepatic metastases, either previously-treated or not. One lung nodule (< 5 mm) is allowed. Calcified lung micronodules as well as typical intra-pulmonary lymph nodes are allowed. Hepatic hilum lymph node < 10 mm (short axis) is allowed.\n- •\tPrior surgery of HCC with micro- or macro-vascular invasion demonstrated at pathology.\n- •\tPrior 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]).\n- •\tPatients with uncontrolled HBV infection and viral load above 500 IU/mL.\n- •\tUntreated or incompletely treated oesophageal and/or gastric varices with bleeding or high risk for bleeding. Unless both pathological analyses showed the absence of cirrhosis and MR scan showed the absence of varices (absence of portal hypertension on imaging), 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 enrolment. Patients who have undergone an EGD within 6 months prior to initiation of study treatment do not need to repeat the procedure\n- •\tPast 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\n- •\tKnown history or symptomatic meningeal tumors\n- •\tGrade 3 (severe) hypertension ≥160 and/or ≥100 mmHG (systolic and diastolic, according to NCI-CTCAE v5.0)\n- •\tPatients with phaeochromocytoma\n- •\tOngoing infection: Hepatitis B is allowed if no active replication is present (HBV replication below 500 IU/mL) or Hepatitis C is allowed if no antiviral treatment is required\n- •\tClinically significant bleeding NCI-CTCAE version 5.0 ≥ Grade 3 within 30 days before enrolment (transfusion indicated)\n- •\tArterial or venous thrombotic or embolic events such as cerebrovascular accident, deep vein thrombosis or pulmonary embolism within 6 months before enrolment\n- •\tAny 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\n- •\tKnown history of human immunodeficiency virus (HIV) infection\n- •\tSeizure disorder requiring medication\n- •\tNon-healing wound, ulcer or bone fracture\n- •\tBreast feeding\n- •\tPregnancy\n- •\tLegal incapacity (persons in custody or under guardianship)\n- •\tDeprived of liberty Subject (by judicial or administrative decision)\n- •\tpatient under curatorship"}

Primary endpoints

• {"endpoint_text":"- 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. Patients will be followed by MRI, 3, 6, 9, 12, 15, 18, 21and 24 months after randomization","definition_or_measurement_approach":"Recurrence defined as recurrence or death, whichever occurs first; radiological criteria: emergence of ≥1 cm nodules with arterial enhancement followed by washout at portal/late phase on MRI, or atypical nodule with histology consistent with HCC; extrahepatic metastasis counts as recurrence. Follow-up MRI schedule at months 3, 6, 9, 12, 15, 18, 21 and 24 after randomization."}

Other endpoints

• {"endpoint_text":"- •\tTo compare RFS at 2 years according to independent central review\n- •\tTo evaluate the compliance to neoadjuvant and adjuvant treatments\n- •\tTo 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\n- •\tTo compare health-related quality of life (HRQoL) in experimental arm vs. control arm\n- •\tTo compare incidences of local-, intrahepatic- and extrahepatic recurrence in experimental arm vs. control arm\n- •\tTo compare time-to-recurrence in experimental arm vs. control arm\n- •\tTo compare overall survival in experimental arm vs. control arm\n- •\tTo compare OS rate at 3 and 5 years after randomization\n- •\tTranslational research (please find details here after)","definition_or_measurement_approach":"Secondary objectives include comparison of RFS by independent central review, treatment compliance, safety/tolerance of neo-adjuvant and adjuvant regimens, HRQoL comparison, recurrence incidence comparisons, time-to-recurrence, overall survival and OS rates at 3 and 5 years; translational research details referenced in protocol. Specific measurement methods not provided in the available extract."}

France

Earliest CTIS Part Ii Submission Date

15-11-2024

Latest Decision Or Authorization Date

20-11-2024

Processing Time Days

5

Number Of Sites

21

Number Of Participants

202

Primary sponsor

Full Name

Centre Hospitalier Universitaire De Montpellier

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"Roche","duties_or_roles":"Source of monetary support","organisation_type":""}