LENVABLA Lenvatinib in neo-adjuvant and adjuvant therapy for poor-prognosis BCLC A HepatoCellular Carcinoma treated by percutaneous ablation procedure in a curative intent: multicentre pilot therapeutic trial

Phase 2

Not yet recruiting

• Conditions: Patients with Biopsy-proven or radiologically-suggested BCLC A HCC eligible for PA and comprising at least one of the following criteria: - Single tumour>3 cm≤ 5cm or - multiple tumours (max 3 lesions ≤ 3cm) or - Single tumour between 2 and 3 cm with at least one of the following characteristic: • Serum AFP>100 ng/mL • Infiltrative form • Macro-trabecular subtype (if applicable)

• Registration Number: 2024-514606-31-00
• Lead Sponsor: Assistance Publique Hopitaux De Paris

Brief Summary

To assess local recurrence-free survival during a 1-year follow-up after PA procedure.

Detailed Description

Not available

Study Timeline

• Study First Posted: 2024-10-29
• Last Update Posted: 2024-10-29

Recruitment & Eligibility

• Status: Authorised, recruitment pending
• Sex: Not specified
• Target Recruitment: 50

Inclusion Criteria

Male or female patients ≥ 18 years

Adequate bone marrow, liver and renal function as assessed by the following laboratory tests: o Hemoglobin > 8.5 g/dL o Absolute neutrophil count ≥ 1500/mm3 (≥ 1200/mm3 for black/African, American) o Platelet count ≥ 60,000/ mm3 o Total bilirubin ≤ 2 mg/dL o Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x upper limit of normal (ULN) o Serum creatinine ≤ 1.5 x ULN o Prothrombine time-international normalized ratio (PT-INR) < 2.3 and PTT < 1.5 o Glomerular Filtration Rate (GFR) ≥ 30 mL/min/1.73 m2

Life expectancy ≥ 3 months

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

Patients affiliated to a Social Security System

Written informed consent signed

Patient under guardianship or curatorship

Satisfactory nutritional status (BMI>18 kg/m² for patients under 70 years old, or ≥21 kg/m² for the patients over 70 years old)

Histological or radiological diagnosis of HCC, whether new or recurrent following a prior curative therapeutic management > 6 months.

Barcelona Clinical Liver Cancer(BCLC) stage Category A

• Single tumour>3 cm≤ 5cm or - Multiple tumours (max 3 lesions ≤ 3cm) or - Single tumour between 2 and 3 cm with at least one of the following characteristic: - Serum AFP>100 ng/mL - Infiltrative form - Macro-trabecular subtype (if applicable)

Patients with HCC amenable for PA as assessed by multidisciplinary board corresponding to the following extension: o Uninodular HCC≥ 2 cm and ≤ 5 cm, no macroscopic vascular invasion o Multinodular maximum 3 nodules ≤ 3 cm, no macroscopic vascular invasion

At least one uni-dimensional measurable lesion by computed tomography (CT) scan or magnetic resonance imaging (MRI) according to modified RECIST for HCC

Absence of any portal vein thrombosis

Liver function status Child-Pugh Class A

Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1

Exclusion Criteria

Patients with recurrence of HCC occurring less than six months after a curative treatment regarded as successful

Congestive heart failure New York Heart Association (NYHA) ≥ class 2

Unstable angina or myocardial infarction within the past 6 months before enrolment

Uncontrolled blood pressure to systolic BP >140mmHg or diastolic BP >90 mmHg in spite of an optimized regimen of antihypertensive medication.

Patients with phaeochromocytoma

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)

Persistent proteinuria of NCI-CTCAE version 4.0 ≥ Grade 3

Ongoing infection > Grade 2 according to NCI-CTCAE version 4.0

Active hepatitis B is allowed if the patient is under antiviral therapy

Clinically significant bleeding NCI-CTCAE version 4.0 ≥ Grade 3 within 30 days before enrolment

Any psychological, familial, sociological, geographical or illness or medical condition that could jeopardize the safety of the patient and/or his compliance with the study protocol and follow-up procedure

•      BCLC stage >A (1 single lesion >5cm or more than 3 lesions ore multifocal HCC >3cm or vascular invasion or extra-hepatic spread)
  

Non-healing wound, ulcer or bone fracture

Known hypersensitivity to the study drug or excipients in the formulation

Any malabsorption condition

Breast feeding

Pregnancy

Patient unable to swallow oral medication

•        Patients with contraindications to PA *Pacemakers or patients who have a history of cardiac arrhythmias or irregular heartbeats (in case of electroporation procedure) *Ascites *Coagulopathy *Ongoing bacterial infection
  

Patients with contraindication to contrast medium intravenous injection either gadolinium or iodinate

Prior liver transplantation

Prior systemic treatment for HCC (chemotherapy, any other TKI, immunotherapy)

Patients with large esophageal varices at risk of bleeding that are not being treated with conventional medical intervention

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

Major surgical procedure or significant traumatic injury within 28 days before enrolment

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
One-year local recurrence-free survival (potentially compared with historical controls, see references)		One-year local recurrence-free survival (potentially compared with historical controls, see references)

Secondary Outcome Measures

Name	Time	Method
- Per nodule assessment of early response (one month) after PA		- Per nodule assessment of early response (one month) after PA
- Per nodule assessment of local recurrence		- Per nodule assessment of local recurrence
- Per nodule assessment of intra segmental distant recurrence		- Per nodule assessment of intra segmental distant recurrence
- Per nodule assessment of extra segmental distant recurrence		- Per nodule assessment of extra segmental distant recurrence
- Assessment of overall recurrence-free survival at 1 and 2 years		- Assessment of overall recurrence-free survival at 1 and 2 years
- Evaluation of the safety of lenvatinib administered as neo and adjuvant therapy		- Evaluation of the safety of lenvatinib administered as neo and adjuvant therapy
- Study of tumour and non-tumour histological/molecular predictors of therapeutic response and resistance based on sequential biopsies performed before and after neo-adjuvant phase then in case of recurrence (if applicable).		- Study of tumour and non-tumour histological/molecular predictors of therapeutic response and resistance based on sequential biopsies performed before and after neo-adjuvant phase then in case of recurrence (if applicable).
- Compliance to lenvatinib treatment		- Compliance to lenvatinib treatment
- Consittution of a sequential biobank comprising liver tissue (if applicable) and peripheral samples (serum, plasma)		- Consittution of a sequential biobank comprising liver tissue (if applicable) and peripheral samples (serum, plasma)

Trial Locations

Locations (7)

Assistance Publique Hopitaux De Paris; 🇫🇷 Paris, France

Centre Hospitalier Universitaire De Montpellier; 🇫🇷 Montpellier Cedex 5, France

Centre Hospitalier Universitaire De Bordeaux; 🇫🇷 Pessac, France

Centre Hospitalier Universitaire Grenoble Alpes; 🇫🇷 Grenoble Cedex 9, France

Centre Hospitalier Universitaire D'Angers; 🇫🇷 Angers, France

Centr Georges Francois Leclerc; 🇫🇷 Dijon, France

Les Hopitaux Universitaires De Strasbourg; 🇫🇷 Strasbourg, France

Assistance Publique Hopitaux De Paris

🇫🇷Paris, France

Matthias BARRAL

Site contact

0156016887

matthias.barral@aphp.fr

Giuliana Amaddeo

Site contact

0149812111

guiliana.amaddeo@aphp.fr

Manon ALLAIRE

Site contact

0142177622

Manon.allaire@aphp.fr

Pierre NAHON

Site contact

0148026280

pierre.nahon@aphp.fr

Mohamed BOUATTOUR

Site contact

0140875614

mohamed.bouattour@aphp.fr

Stanislas POL

Site contact

0158413001

stanislas.pol@aphp.fr

Violaine OZENNE

Site contact

0149282380

violaine.ozenne@aphp.fr