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

NCT05901194 | Active Not Recruiting Phase 1 DMC

• 2 other identifiers: APHP2202672022-000998-31
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 6

Brief 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.

Conditions

Hepatocellular Carcinoma Non-resectable

Keywords

Liver transplantation; non resectable hepatocellular carcinoma

Outcome Measures

Primary Outcomes (1)

• The proportion of patients with lenvatinib who have a Liver transplantation (LT)

  The proportion of patients with TACE failure and treated with lenvatinib who have a LT

  12 months

Secondary Outcomes (6)

• Time to progression under lenvatinib

  up to 12 months and until LT

• Progression under lenvatinib

  up to 12 months and until LT

• Response rate

  up to 12 months and until LT

• Response rate

  after the LT, during 18 months

• Recurrence rate

  after LT, during 18 months

Study Arms (1)

Lenvatinib

EXPERIMENTAL

Lenvatinib will be administred orally and daily at the usual dose ( 8 or 12 mg per day depending on the weight \< or ≥ 60kg) in the 25 patients of the study from TACE failure until LT

Drug: Lenvatinib

Interventions

Lenvatinib DRUG

Lenvatinib will be administred orally and daily at the usual dose ( 8 or 12 mg per day depending on the weight \< or ≥ 60kg) in the 25 patients of the study from TACE failure until LT

Lenvatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• Contraindication of lenvatinib and excipient
• 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)
• 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)
• Coagulopathy
• 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
• Advanced or Metastatic HCC (BCLC C)
• Persistent proteinuria of NCI-current CTCAE ≥ Grade ≥ Grade 3

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Laboratoire EISAI: collaborator

Study Sites (6)

Hospital Haut levêque

Bordeaux, France

Location

Hospital Henri Mondor

Créteil, France

Location

Hospital Claude Huriez

Lille, France

Location

Pontchaillou Hospital

Rennes, France

Location

Hospital Trousseau

Tours, France

Location

Paul Brousse Hospital

Villejuif, France

Location

MeSH Terms

Interventions

lenvatinib

Study Officials

• Olivier ROSMORDUC

  APHP, Paul Brousse Hospital, villejuif, France

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2023
• First Posted: June 13, 2023
• Study Start: July 10, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: April 7, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (6)