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

• Status: Not yet recruiting
• Trial end date: 2027-07-01
• Target enrollment: 0
• Participant gender: All

Summary

Currently in France, hepatocellular carcinoma (HCC) represents over 30% of indications of liver transplantation (LT) (# 500 cases/year). Chemoembolization (TACE) is the most commonly used bridge treatment in those patients (estimate 60%). These patients will present with a complete response in only 60 % of the cases (# 180 patients per year in France) and failure in 40 % of the cases (# 120 patients per year in France).

A systemic treatment using lenvatinib might provide a benefit in patients presenting with a non-resectable HCC in waiting list for LT and with a TACE failure (i.e. those with an active disease and a partial response or a stable disease or a progressive disease on imaging data, in particular when AFP remains significantly increased after 2 TACE) by decreasing dropout rate before LT and decreasing recurrence rate post-LT without new safety signal.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborator: Laboratoire EISAI
• Treatments: Lenvatinib

Criteria

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