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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Not possible to specify

Trial duration

29 Oct 2024 → ongoing

Decision date (initial)

2024-10-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Laboratoire EISAI

External identifiers

EU CT number

2024-514606-31-00

EudraCT number

2020-005504-18

ClinicalTrials.gov

NCT05113186

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

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

Secondary objectives 5

1. - To assess the changes of tumorous and non-tumorous perfusion parameters observed with MRI after of neoadjuvant treatment, and before the PA procedure
2. -To assess the incidences of intra segmental/ extra segmental distant recurrence
3. - To assess the overall survival at 1 and 2 years following PA procedure
4. - To assess the compliance to neoadjuvant and adjuvant treatments
5. - To assess the tolerance of lenvatinib in the setting of neo- and adjuvant therapy to PA

Conditions and MedDRA coding

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)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 17

1. Male or female patients ≥ 18 years
2. Histological or radiological diagnosis of HCC, whether new or recurrent following a prior curative therapeutic management > 6 months.
3. Barcelona Clinical Liver Cancer(BCLC) stage Category A
4. - 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)
5. 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
6. At least one uni-dimensional measurable lesion by computed tomography (CT) scan or magnetic resonance imaging (MRI) according to modified RECIST for HCC
7. Absence of any portal vein thrombosis
8. Liver function status Child-Pugh Class A
9. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1
10. 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
11. Life expectancy ≥ 3 months
12. Women of childbearing potential (WOCBP) need to accept one effective method of contraception until 1 month after the last lenvatinib intake and avoid pregnancy
13. 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
14. Patients affiliated to a Social Security System
15. Written informed consent signed
16. Patient under guardianship or curatorship
17. Satisfactory nutritional status (BMI>18 kg/m² for patients under 70 years old, or ≥21 kg/m² for the patients over 70 years old)

Exclusion criteria 25

1. Patients with recurrence of HCC occurring less than six months after a curative treatment regarded as successful
2. - BCLC stage >A (1 single lesion >5cm or more than 3 lesions ore multifocal HCC >3cm or vascular invasion or extra-hepatic spread)
3. - 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
4. Patients with contraindication to contrast medium intravenous injection either gadolinium or iodinate
5. Prior liver transplantation
6. Prior systemic treatment for HCC (chemotherapy, any other TKI, immunotherapy)
7. Patients with large esophageal varices at risk of bleeding that are not being treated with conventional medical intervention
8. 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
9. Major surgical procedure or significant traumatic injury within 28 days before enrolment
10. Congestive heart failure New York Heart Association (NYHA) ≥ class 2
11. Unstable angina or myocardial infarction within the past 6 months before enrolment
12. Uncontrolled blood pressure to systolic BP >140mmHg or diastolic BP >90 mmHg in spite of an optimized regimen of antihypertensive medication.
13. Patients with phaeochromocytoma
14. 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)
15. Persistent proteinuria of NCI-CTCAE version 4.0 ≥ Grade 3
16. Ongoing infection > Grade 2 according to NCI-CTCAE version 4.0
17. Active hepatitis B is allowed if the patient is under antiviral therapy
18. Clinically significant bleeding NCI-CTCAE version 4.0 ≥ Grade 3 within 30 days before enrolment
19. 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
20. Non-healing wound, ulcer or bone fracture
21. Known hypersensitivity to the study drug or excipients in the formulation
22. Any malabsorption condition
23. Breast feeding
24. Pregnancy
25. Patient unable to swallow oral medication

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. One-year local recurrence-free survival (potentially compared with historical controls, see references)

Secondary endpoints 9

1. - Per nodule assessment of early response (one month) after PA
2. - Per nodule assessment of local recurrence
3. - Per nodule assessment of intra segmental distant recurrence
4. - Per nodule assessment of extra segmental distant recurrence
5. - Assessment of overall recurrence-free survival at 1 and 2 years
6. - Evaluation of the safety of lenvatinib administered as neo and adjuvant therapy
7. - 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).
8. - Compliance to lenvatinib treatment
9. - Consittution of a sequential biobank comprising liver tissue (if applicable) and peripheral samples (serum, plasma)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Investigator

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Investigator

Locations

1 EU/EEA country · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications