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

Hepatocellular Carcinoma Non-resectable Clinical Trial

— Ta-Len-Tra  

Official title:

Study of the Benefit of Lenvatinib Treatment in Waiting List of Liver Transplantation After TACE Failure in Patients With Hepatocellular Carcinoma (HCC)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05901194
• Other study ID #: APHP220267
• Secondary ID: 2022-000998-31
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: June 2023
• Est. completion date: July 2027

Study information

• Verified date: May 2023
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Olivier ROSMORDUC
• Phone: +336 19 35 71 56
• Email: olivier.rosmorduc[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The investigators identified a sub-group of patients with non resectable HCC that could benefit from a systemic neoadjuvant medical strategy before liver transplantation (LT). In these patients, the investigators propose to add oral systemic chemotherapy with lenvatinib as a bridging/downstaging therapeutic approach until LT. In the case of at least partial response or stability under lenvatinib and within AFP score of 2, the patients will be transplanted and lenvatinib will be stopped on the day or the day before LT (depending on the availability of the graft). In the case of disease progression, the patient will stop prematurely the lenvatinib treatment and will be treated according to usual practices. The patient's eligibility for LT will be assessed according to usual practices.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 25
• Est. completion date: July 2027
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma Non-resectable

Intervention

Drug:
• Lenvatinib
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

Locations

Country	Name	City	State
France	Hospital Haut levêque	Bordeaux
France	Hospital Henri Mondor	Créteil
France	Hospital Claude Huriez	Lille
France	Pontchaillou Hospital	Rennes
France	Hospital Trousseau	Tours
France	Paul Brousse Hospital	Villejuif

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Laboratoire EISAI

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Time to progression under lenvatinib	Time to progression under lenvatinib before LT by imaging. Progression will be based on RECIST and mRECIST	up to 12 months and until LT
Secondary	Progression under lenvatinib	Progression under lenvatinib before LT by imaging. Progression will be bases on RECIST and mRECIST	up to 12 months and until LT
Secondary	Response rate	Response rate before LT by imaging	up to 12 months and until LT
Secondary	Response rate	Response rate by liver specimen pathology after the LT	after the LT, during 18 months
Secondary	Recurrence rate	Recurrence rate after LT by imaging	after LT, during 18 months
Secondary	Incidence of Treatment-Emergent Adverse Events	Incidence of Treatment-Emergent Adverse Events using current CTCAE	Throughout the study, an average of 31 months