Lenvatinib Treatment in Waiting List of Liver Transplantation After TACE Failure in Patients With Hepatocellular Carcinoma

Inclusion Criteria:

* Non resectable HCC
* Initial French AFP score \< or = 2
* Registered on national waiting list for LT
* Who underwent TACE as a bridge to LT
* 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
* 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.

Exclusion Criteria:

* 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
* Known hypersensitivity to the study drug or excipients in the formulation
* Decompensated cirrhosis (Child-Pugh \> A6)
* 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)
* Advanced or Metastatic HCC (BCLC C)
* Persistent proteinuria of NCI-current CTCAE ≥ Grade ≥ Grade 3
* Project of living donor
* Pregnant or lactating woman
* Curator or guardianship or patient placed under judicial protection
* Participation in other interventional research during the study.
* History within the past 3 months before enrollment of haemorrhage, gastrointestinal perforation, gastrointestinal or non-gastrointestinal fistula,
* History of aneurism,
* Hypokalemia, hypomagnesemia and hypocalcemia