Patients with a non resectable HCC registered on national waiting list for LT with no complete response to TACE as a bridging loco-regional treatment. MedDRA version: 21.0 Level: LLT Classification code 10019828 Term: Hepatocellular carcinoma non-resectable System Organ Class: 100000004864
Conditions
Interventions
Trade Name: LENVIMA 4 mg, Capsules
Product Name: LENVATINIB
Product Code: L01XE29
Pharmaceutical Form: Capsule
INN or Proposed INN: LENVATINIB
CAS Number: 417716-92-8
Concentration unit: mg milligram(
Sponsors
ASSISTANCE PUBLIQUE-HOPITAUX DE PARIS (AP-HP)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patient presenting with - Non resectable HCC - Initial French AFP score 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) =65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
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 .
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To estimate the proportion of LT among patients under lenvatinib with no complete response after 2 TACE.;Secondary Objective: - To estimate time to progression under lenvatinib and until LT - To compare progression rate under lenvatinib and until LT with the theorical proportion of 20%. - To estimate the response rate by imaging before LT - To estimate the response rate by liver specimen pathology after LT - To estimate the recurrence rate after LT - To demonstrate the safety of this sequential strategy - Characterization of immune cell population of peripheral change under treatment.;Primary end point(s): The proportion of patients with TACE failure and treated with lenvatinib who have a LT.;Timepoint(s) of evaluation of this end point: At the time of the LT | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Time to progression under lenvatinib before LT by imaging. Progression will be based on RECIST and mRECIST. - Progression under lenvatinib before LT by imaging. Progression will be based on RECIST and mRECIST. - Response rate before LT by imaging - Response rate by liver specimen pathology after the LT - Recurrence rate after LT by imaging - Evaluate Safety by AE and SAE (using current CTCAE ) The endpoints associated to the immunophenotyping of peripheral blood immune cell population will be on the ancillary analyses.;Timepoint(s) of evaluation of this end point: - within 12 months of treatment for imaging and safety and immunophenotyping - at the time of transplantation for histological characterization - within 18 months after LT for imaging recurrence. | — |
Countries
France
Contacts
Public ContactMyriem CARRIER
ASSISTANCE PUBLIQUE-HOPITAUX DE PARIS (AP-HP)
Outcome results
None listed