Study of the Benefit of Lenvatinib Treatment in Waiting List of Liver Transplantation After TACE Failure in Patients With Hepatocellular Carcinoma (HCC)
Overview
- Phase
- Phase 1
- Intervention
- Lenvatinib
- Conditions
- Hepatocellular Carcinoma Non-resectable
- Sponsor
- Assistance Publique - Hôpitaux de Paris
- Enrollment
- 25
- Locations
- 6
- Primary Endpoint
- The proportion of patients with lenvatinib who have a Liver transplantation (LT)
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
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.
Detailed 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.
Investigators
Eligibility 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:
Exclusion Criteria
- •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
Arms & Interventions
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
Intervention: Lenvatinib
Outcomes
Primary Outcomes
The proportion of patients with lenvatinib who have a Liver transplantation (LT)
Time Frame: 12 months
The proportion of patients with TACE failure and treated with lenvatinib who have a LT
Secondary Outcomes
- Time to progression under lenvatinib(up to 12 months and until LT)
- Response rate(after the LT, during 18 months)
- Progression under lenvatinib(up to 12 months and until LT)
- Recurrence rate(after LT, during 18 months)
- Incidence of Treatment-Emergent Adverse Events(Throughout the study, an average of 31 months)