NCT05113186: LENVABLA

Neoadjuvant and Adjuvant Lenvatinib in HCC Patients Treated by Percutaneous Ablative

Active, enrolled Phase 2 Last updated 29 January 2026

What this trial tests

Phase 2 trial testing Lenvatinib Pill in Hepatocellular Carcinoma in 32 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

2 February 2022

Primary endpoint
19 June 2025

2 October 2026

Quick facts

Lead sponsor	Assistance Publique - Hôpitaux de Paris
Phase	Phase 2
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	32
Start date	2 February 2022
Primary completion	19 June 2025
Estimated completion	2 October 2026
Sites	1 location across France

Drugs / interventions tested

• Lenvatinib Pill — full drug profile →

Conditions studied

• Hepatocellular Carcinoma — all drugs for Hepatocellular Carcinoma →

Sponsor

Assistance Publique - Hôpitaux de Paris — full company profile →

Who can join

Adults 18 to 99, any sex, with Hepatocellular Carcinoma. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Percutaneous ablation (PA) is the only non-surgical curative treatment of hepatocellular carcinoma (HCC). Due to its excellent tolerance, particularly in patients with portal hypertension or bearing comorbidities, it now represents in France nearly 70% of the first-line curative treatment of "in Milan" tumours. For HCC less than 3 cm, ideal indication for percutaneous ablations, results of monopolar radiofrequency ablation (mRFA), are excellent with only 5% of reported non-tumoral control after a first procedure. In addition to mRFA the arsenal of ablations has grown considerably with the emergence of new techniques which allow the expansion of indications for PA, especially in patients with poor prognostic tumors or relatively advanced beyond the Milan criteria. In this setting, multibipolar mode using no touch technique (mbpRFAnt) increases the tumour volume than can be ablated, allowing the removal of large tumors\> 5 cm. Inadequate tumour control is then de facto greater in these situations, around 20%. Difficult-to-access tumors can furthermore be treated by percutaneous irreversible electrotroporation (IRE).

Despite a tumor burden accessible for curative ablation, a phenotype of "aggressive" HCC characterized by high rates of local recurrences is yet to be defined. Up to now, several characteristics might define this subtype with a poor-prognosis and include 1) high serum alpha-foetoprotein (AFP) levels, 2) radiological infiltrative form, and 3) histological macrotrabecular subtype. Based on these characteristics, median recurrence-free survival of these patients is usually below 10 months.

High serum AFP level is a well-known predictor of HCC recurrence following curative procedure. In patients treated by percutaneous ablation, regardless of the technique used and irrespective of tumor burden, high baseline serum AFP level has tenaciously been reported as an independent predictor or recurrence..

More recently, the radiological description of infiltrative HCC (as opposed to mass-forming) has been identified as an aggressive from of HCC with a poor prognosis even when eligible for ablation. This aspect is often associated with infra-clinical invasion of the portal veins (PV), leading to poor prognosis. Finally, a "massive macrotrabecular" (MTM) histological subtype of HCC associated with specific molecular features has recently been described. This MTM-HCC subtype, reliably observed in 12% of patients eligible for curative treatment, represents an aggressive form of HCC is an independent predictor of early and overall recurrence following PA, which is retained even after patient stratification according to common clinical, biological, and pathological features of aggressiveness.

The idea of optimizing HCC curative treatments using adjuvant biotherapy, particularly in patients with poor-prognosis tumors in curative intent, is particularly attractive. One trial in adjuvant setting was conducted, the STORM trial, that tested the benefit of sorafenib in curative intent of in Milan HCC. This negative trial included patients within Milan HCC, with an expected low rate of recurrence with only few patients treated by PA.

Lenvatinib is a multikinase inhibitor which has been recently approved as firs-line therapy for advanced HCC. The investigators assume that lenvatinib could have also a synergistic local action with PA in two ways. First, given as neoadjuvant regimen, lenvatinib by reducing tumor and liver perfusion could decrease the global heat sink effect associated with loco-regional blood microcirculation during PA. Second, by carrying on in adjuvant treatment, lenvatinib could decrease the magnitude of non-specific inflammatory angiogenesis around the treatment zone, therefore reducing the risk of locoregional (intrasegmental) cells tumor spreading or promotion.

Given the dismall prognosis of the aforementioned poor-prognosis HCC eligible for PA with an overall median recurrence-free survival below 10 months, the investigators hypothesis is that addition of Lenvatinib as neo- and adjuvant therapy might increase tumour control in these difficult-to-treat patients. Patients combining either high serum AFP levels, infiltrative form or MTM-HCC histological subtype represent 30% of BCLC A stage HCC patients in expert centers, and are the ideal candidates for such trials.

Therefore, the first aim of this proposal is to assess the benefit of lenvatinib in neo- and adjuvant setting combined with curative percutaneous ablation for BCLC A HCC patients considered at high risk of local recurrence (high AFP or infiltrative form or macrotrabecular massive subtype).

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. Management of Hepatocellular Carcinoma in 2024: The Multidisciplinary Paradigm in an Evolving Treatment Landscape.
   Kinsey E, Lee HM. · · 2024 · cited 68× · PMID 38339417 · DOI 10.3390/cancers16030666
2. Molecular and immune landscape of hepatocellular carcinoma to guide therapeutic decision-making.
   Dhanasekaran R, Suzuki H, Lemaitre L, Kubota N, et al · · 2025 · cited 42× · PMID 37300379 · DOI 10.1097/hep.0000000000000513
3. The evolving role of lenvatinib at the new era of first-line hepatocellular carcinoma treatment.
   Chan LL, Chan SL. · · 2023 · cited 20× · PMID 37226446 · DOI 10.3350/cmh.2023.0114
4. Molecular and immune landscape of hepatocellular carcinoma for therapeutic development.
   Suzuki H, Mishra S, Paul S, Hoshida Y. · · 2025 · cited 8× · PMID 39639434 · DOI 10.17998/jlc.2024.12.02
5. Small-molecule-based targeted therapy in liver cancer.
   Ming Y, Gong Y, Fu X, Ouyang X, et al · · 2024 · cited 6× · PMID 39113358 · DOI 10.1016/j.ymthe.2024.08.001
6. Neoadjuvant systemic therapy for hepatocellular carcinoma: challenges and opportunities-a narrative review.
   Zhang Y, Yue S, Zhang B, Chen X, et al · · 2025 · cited 2× · PMID 41104208 · DOI 10.21037/hbsn-24-175
7. Advancing Adjuvant Immunotherapy in Hepatocellular Carcinoma: A Comprehensive Review.
   Akabane M, Chatzipanagiotou OP, Imaoka Y, Schenk A, et al · · 2025 · cited 1× · PMID 40589998 · DOI 10.2147/itt.s528709