Study of the benefit of lenvatinib treatment in waiting list of liver transplantation after TACE failure in patients with hepatocellular carcinoma (HCC) : Ta-Len-Tra

Prior treatment

• History within the past 3 months before enrollment of haemorrhage, gastrointestinal perforation, gastrointestinal or non-gastrointestinal fistula
• Prior systemic therapy with oral TKI and/or immunotherapy
• 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
• Recent digestive bleeding associated with portal hypertension (whithin the 3 months prior to inclusion in the study)

Other illness

• History of aneurism
• Known hypersensitivity to the study drug or excipients in the formulation

Lab values

• Contraindication of lenvatinib and excipient: 1) Cardiovascular: - Rhythmic or ischemic recent or uncontrolled cardiac disease: Pacemakers or patients who have a history of cardiac arrhythmias or irregular heartbeats (in case of electroporation procedure) - Congestive heart failure New York Heart Association (NYHA) ≥ class 2 - Unstable angina or myocardial infarction within the past 6 months before enrolment - Uncontrolled arterial hypertension (systolic ≥ 140 mmHg, diastolic ≥ 90 mmHg) 2) Ongoing ascites: 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) 3) Coagulopathy 4) Ongoing infection > Grade 2 according to NCI-current CTCAE . Hepatitis B is allowed if no active replication is present (below 100 IU/mL). Hepatitis C is allowed if no antiviral treatment is ongoing

Other

• Pregnant or lactating woman
• Curator or guardianship or patient placed under judicial protection
• Participation in other interventional research during the study
• Hypokalemia, hypomagnesemia and hypocalcemia
• Decompensated cirrhosis (Child-Pugh > A6)
• Advanced or Metastatic HCC (BCLC C)
• Persistent proteinuria of NCI-current CTCAE ≥ Grade ≥ Grade 3
• Project of living donor

• Patient presenting with non resectable HCC
• Adequate bone marrow, liver and renal function as assessed by the following laboratory tests: - Hemoglobin > 8.5 g/dL - Absolute neutrophil count ≥ 1500/mm3 (≥ 1200/mm3 for black/African, American) - Platelet count ≥ 60,000/ mm3 - Total bilirubin ≤ 2 mg/dL or 34 mcmol/l - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x upper limit of normal (ULN) - Serum creatinine ≤ 1.5 x ULN - Prothrombine time-international normalized ratio (PT-INR) < 2.3 and PTT < 50 % - Glomerular Filtration Rate (GFR) ≥ 30 mL/min/1.73 m2
• Patient with QT/QTc < 480 ms
• Women of childbearing potential (WOCBP) need to accept one effective method of contraception until 1 month after the last lenvatinib intake and avoid pregnancy
• 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
• Initial French AFP score < or = 2
• Registered on national waiting list for LT
• Who underwent TACE as a bridge to LT (i.e. persistent active disease, including stable disease or partial response or progression)
• With no complete response after 2 TACE (i.e. persistent active disease, including stable disease or partial response or progression)
• Non eligible for percutaneous ablation
• Informed, written consent obtained from the patient
• Having the rights to French social insurance
• Aged of 18 years or older