Hepatocellular carcinoma (HCC) is a common tumor (the 8th leading cause of cancer in France) and has a poor prognosis. It is the 3rd leading cause of cancer deaths in the world. In the early stages (low tumor mass), HCC can be treated for curative purposes by surgical resection, percutaneous ablation or liver transplantation. When the tumor mass is larger (> 3 nodules) but remains confined to the liver, the standard treatment is hepatic intra-arterial chemoembolization (TACE). In the event of failure of the latter or if the tumor dissemination progresses in the portal venous system or in the form of metastases, the systemic treatments are then indicated.

In 1st line, the reference treatment is a tyrosine kinase inhibitor (ITK) Sorafenib.

Cabozantinib obtained the European and French authorization (AMM) in November 2018 for its use in case of failure of Sorafenib in patients with HCC.

The main objective is the evaluation of the safety of Cabozantinib administered to patients with intermediate HCC ineligible for chemoembolization or advanced HCC after failure of Sorafenib and possibly another systemic anticancer line.

Inclusion Criteria:

• Major patient (age ≥ 18 years).
• Patient with a histologically proven HCC, or by radiology if cirrhotic liver (according to international recommendations).

Patient with stage B BCLC classification after failure or impossibility of transarterial chemoembolization (TACE), or advanced stage C having already received one to two systemic lines, including one by Sorafenib.

• eastern cooperative oncology group score of 0 or 1 (ECOG).
• Child-Pugh A5 or A6 score.
• Disease evaluable by RECIST v1.1 and mRECIST.
• Hemoglobin> 8.5g / dL.
• Platelets> 60 giga / L.
• neutrophils> 1.2 giga / L.
• ALAT and ASAT <5N
• Patient having a normal magnesium level
• Clearance with creatinine> 40ml / min (by the MDRD formula).
• For patients who have had radiotherapy on the liver: a wash out of at least one month before the start of the treatment under study must be respected.
• For patients who have had a radioembolization a wash out of at least three months before the beginning of the treatment under study must be respected.
• Patient who agreed to participate in the study and signed the informed consent.
• Patient affiliated to a social security scheme.

Exclusion Criteria:

• Patient with another cancer not cured or whose complete remission has been obtained for less than 2 years compared to the date of inclusion in CLERANCE.
• Patients eligible for surgical resection or radiofrequency ablation or liver transplantation or TACE according to international recommendations.
• Patient who has already had more than two lines of systemic treatment for his HCC (tyrosine kinase inhibitor, intravenous cytotoxic chemotherapy, immunotherapy, hormonal therapy for HCC).
• Patient who has never received Sorafenib in his previous systemic line (s).
• Patient who has already received a c-MET inhibitor.
• Patient with chronic viral B infection known not treated with a nucleoside / nucleotide analogue.
• Patients infected with HIV known (even if it is viro-suppressed by anti-retroviral treatments).
• Patients with or at risk for severe bleeding (a gastroscopy should be performed every two years if the patient doesn't have varicose veins and every year if the patient has varicose vein).
• Patients with inflammatory bowel diseases (Crohn's disease, ulcerative colitis, peritonitis, diverticulitis, appendicitis)
• Patient with galactose intolerance or Lapp lactase deficiency, or glucose or galactose malabsorption syndrome.
• Patients with tumor infiltration of the digestive tract with risk of fistulation
• Patients with recent digestive surgery (<1 month) or not yet fully healed.
• Patients with QTcF> 480 ms on inclusion ECG.
• Known hypersensitivity to Cabozantinib or to any of the excipients.
• Pregnant or nursing woman.
• Patient of childbearing age without mechanical contraception.
• Patient placed under safeguard of justice (tutelage or curatorship).
• Patient not benefiting from social security.
• Patient participating in another interventional research in progress or including an exclusion period still in progress at pre-inclusion (except interventional research with minimal risks and constraints that do not interfere with the judgment criteria of the study according to the judgment of the coordinating investigator).

Chronic active C infection is not a contraindication. Treatment with direct antiviral agents is left to the discretion of each investigator, but the viremic or cured status of each patient should be mentioned.