Ignite Creation Date:
2024-05-06 @ 4:51 PM
Last Modification Date:
2024-10-26 @ 2:17 PM
Study NCT ID:
NCT05113186
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-04-09
First Post:
2021-07-31
Brief Title:
Neoadjuvant and Adjuvant Lenvatinib in HCC Patients Treated by Percutaneous Ablative
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
Official Title:
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
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
LENVABLA
Brief Summary:
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
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
Detailed Description:
Multicenter 19 hepatology or hepatoGastroenterology and radiology departments in 11 French hospitals inclusion of patients in 10 centers
A pilot interventional prospective multicenter study
The design of study is summarized as follows
Neoadjuvant phase with lenvatinib for 21 days rationale compromise between expected benefit and acceptable tolerance without compromising ablation procedure
PA of HCC in a curative intent radiofrequency microwave or electroporation
Adjuvant phase with lenvatinib for 3 months rationale compromise between expected benefit and acceptable tolerance without compromising ablation procedure Lenvatinib doses will be adapted according to SmPC
Constitution of a biobank with
paraffin and frozen tumoral and non tumoral biopsy sampled at before and after one month of neoadjuvant lenvatinib second biopsies at the time of the PA procedure
Serum plasma samples before the neoadjuvant lenvatinib before PA procedure at 13 months of the adjuvant lenvatinib and at month 6
A pilot interventional prospective multicenter study
The design of study is summarized as follows
Neoadjuvant phase with lenvatinib for 21 days rationale compromise between expected benefit and acceptable tolerance without compromising ablation procedure
PA of HCC in a curative intent radiofrequency microwave or electroporation
Adjuvant phase with lenvatinib for 3 months rationale compromise between expected benefit and acceptable tolerance without compromising ablation procedure Lenvatinib doses will be adapted according to SmPC
Constitution of a biobank with
paraffin and frozen tumoral and non tumoral biopsy sampled at before and after one month of neoadjuvant lenvatinib second biopsies at the time of the PA procedure
Serum plasma samples before the neoadjuvant lenvatinib before PA procedure at 13 months of the adjuvant lenvatinib and at month 6
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None