Lenvatinib for Hepatocellular carcinoma (BCLC A)

Inclusion criteria

• {"criterion_text":"- Male or female patients ≥ 18 years\n- Adequate 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 (≥ 1200/mm3 for black/African, American) o\tPlatelet count ≥ 60,000/ mm3 o\tTotal bilirubin ≤ 2 mg/dL o\tAlanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x upper limit of normal (ULN) o\tSerum creatinine ≤ 1.5 x ULN o\tProthrombine time-international normalized ratio (PT-INR) < 2.3 and PTT < 1.5 o\tGlomerular Filtration Rate (GFR) ≥ 30 mL/min/1.73 m2\n- Life expectancy ≥ 3 months\n- Women of childbearing potential (WOCBP) need to accept one effective method of contraception until 1 month after the last lenvatinib intake and avoid pregnancy\n- Patients who are sexually active with WOCBP partners need to accept one effective method of contraception until 1 month after lenvatinib intake and men must agree to use adequate contraception\n- Patients affiliated to a Social Security System\n- Written informed consent signed\n- Patient under guardianship or curatorship\n- Satisfactory nutritional status (BMI>18 kg/m² for patients under 70 years old, or ≥21 kg/m² for the patients over 70 years old)\n- Histological or radiological diagnosis of HCC, whether new or recurrent following a prior curative therapeutic management > 6 months.\n- Barcelona Clinical Liver Cancer(BCLC) stage Category A\n- - Single tumour>3 cm≤ 5cm or - Multiple tumours (max 3 lesions ≤ 3cm) or - Single tumour between 2 and 3 cm with at least one of the following characteristic: - Serum AFP>100 ng/mL\t - Infiltrative form - Macro-trabecular subtype (if applicable)\n- Patients with HCC amenable for PA as assessed by multidisciplinary board corresponding to the following extension: o\tUninodular HCC≥ 2 cm and ≤ 5 cm, no macroscopic vascular invasion o\tMultinodular maximum 3 nodules ≤ 3 cm, no macroscopic vascular invasion\n- At least one uni-dimensional measurable lesion by computed tomography (CT) scan or magnetic resonance imaging (MRI) according to modified RECIST for HCC\n- Absence of any portal vein thrombosis\n- Liver function status Child-Pugh Class A\n- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1"}

Exclusion criteria

• {"criterion_text":"- Patients with recurrence of HCC occurring less than six months after a curative treatment regarded as successful\n- - BCLC stage >A (1 single lesion >5cm or more than 3 lesions ore multifocal HCC >3cm or vascular invasion or extra-hepatic spread)\n- - Patients with contraindications to PA *Pacemakers or patients who have a history of cardiac arrhythmias or irregular heartbeats (in case of electroporation procedure) *Ascites *Coagulopathy *Ongoing bacterial infection\n- Patients with contraindication to contrast medium intravenous injection either gadolinium or iodinate\n- Prior liver transplantation\n- Prior systemic treatment for HCC (chemotherapy, any other TKI, immunotherapy)\n- Patients with large esophageal varices at risk of bleeding that are not being treated with conventional medical intervention\n- 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 tumours. Any cancer curatively treated > 3 years prior to study entry is permitted\n- Major surgical procedure or significant traumatic injury within 28 days before enrolment\n- Congestive heart failure New York Heart Association (NYHA) ≥ class 2\n- Unstable angina or myocardial infarction within the past 6 months before enrolment\n- Uncontrolled blood pressure to systolic BP >140mmHg or diastolic BP >90 mmHg in spite of an optimized regimen of antihypertensive medication.\n- Patients with phaeochromocytoma\n- Refractory ascites according to EASL guidelines definition (ascites that cannot be mobilized or the early recurrence of which cannot be prevented because of a lack of response to sodium restriction and diuretic treatment)\n- Persistent proteinuria of NCI-CTCAE version 4.0 ≥ Grade 3\n- Ongoing infection > Grade 2 according to NCI-CTCAE version 4.0\n- Active hepatitis B is allowed if the patient is under antiviral therapy\n- Clinically significant bleeding NCI-CTCAE version 4.0 ≥ Grade 3 within 30 days before enrolment\n- 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\n- Non-healing wound, ulcer or bone fracture\n- Known hypersensitivity to the study drug or excipients in the formulation\n- Any malabsorption condition\n- Breast feeding\n- Pregnancy\n- Patient unable to swallow oral medication"}

Primary endpoints

• {"endpoint_text":"- One-year local recurrence-free survival (potentially compared with historical controls, see references)","definition_or_measurement_approach":"Assess local recurrence-free survival during a 1-year follow-up after the percutaneous ablation (PA) procedure; potentially compared with historical controls."}

Secondary endpoints

• {"endpoint_text":"-\tPer nodule assessment of early response (one month) after PA","definition_or_measurement_approach":"Per-nodule assessment of early response at one month after PA (as stated)."}
• {"endpoint_text":"-\tPer nodule assessment of local recurrence","definition_or_measurement_approach":"Per-nodule assessment of local recurrence (as stated)."}
• {"endpoint_text":"-\tPer nodule assessment of intra segmental distant recurrence","definition_or_measurement_approach":"Per-nodule assessment of intra-segmental distant recurrence (as stated)."}
• {"endpoint_text":"-\tPer nodule assessment of extra segmental distant recurrence","definition_or_measurement_approach":"Per-nodule assessment of extra-segmental distant recurrence (as stated)."}
• {"endpoint_text":"-\tAssessment of overall recurrence-free survival at 1 and 2 years","definition_or_measurement_approach":"Assessment of overall recurrence-free survival at 1 and 2 years following the PA procedure (as stated)."}
• {"endpoint_text":"-\tEvaluation of the safety of lenvatinib administered as neo and adjuvant therapy","definition_or_measurement_approach":"Evaluation of safety/tolerability of lenvatinib when given as neoadjuvant and adjuvant therapy (as stated)."}
• {"endpoint_text":"-\tStudy of tumour and non-tumour histological/molecular predictors of therapeutic response and resistance based on sequential biopsies performed before and after neo-adjuvant phase then in case of recurrence (if applicable).","definition_or_measurement_approach":"Study of histological/molecular predictors of response and resistance using sequential biopsies performed before and after the neoadjuvant phase and at recurrence if applicable (as stated)."}
• {"endpoint_text":"-\tCompliance to lenvatinib treatment","definition_or_measurement_approach":"Assessment of compliance/adherence to lenvatinib treatment (as stated)."}
• {"endpoint_text":"-\tConsittution of a sequential biobank comprising liver tissue (if applicable) and peripheral samples (serum, plasma)","definition_or_measurement_approach":"Creation of a sequential biobank containing liver tissue (if applicable) and peripheral samples (serum, plasma) for correlative studies (as stated)."}

France

Earliest CTIS Part Ii Submission Date

22-07-2024

Latest Decision Or Authorization Date

29-10-2024

Processing Time Days

99

Number Of Sites

13

Number Of Participants

50

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

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