None listed
Conditions
Interventions
Trade Name: LENVIMA 4 mg, Capsules
Product Name: LENVATINIB
Pharmaceutical Form: Capsule
INN or Proposed INN: LENVATINIB
CAS Number: 417716-92-8
Concentration unit: mg milligram(s)
Concentration type:
Sponsors
Assistance Publique – Hôpitaux de Paris (AP-HP)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Male or female patients = 18 years - Histological diagnosis of HCC, whether new or recurrent following a prior curative therapeutic management > 6 months. - Barcelona Clinical Liver Cancer(BCLC) stage Category A - Comprising at least one of the following the following characteristics: - Serum AFP>100 ng/mL - Infiltrative form - Macro-trabecular subtype - 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 - 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) 18 kg/m² for patients under 70 years old, or =21 kg/m² for the patients over 70 years old)der Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: - Patients with recurrence of HCC occurring less than six months after a curative treatment regarded as successful - BCLC stage >A (1 single lesion >5cm or more than 3 lesions ore multifocal HCC >3cm or vascular invasion or extra-hepatic spread) - 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 or candidates for liver transplantation - Prior systemic treatment for HCC (chemotherapy, any other TKI, immunotherapy) - Patients with large oesophageal 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 - 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. Hepatitis B is allowed if no active replication is present (below 100 IU/mL). Hepatitis C is allowed if no antiviral treatment is required - 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 - 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess local recurrence-free survival during a 1 year follow-up after PA procedure. Local recurrence is defined as emergence of irregular areas enhanced at arterial phase followed by washout at portal phase observed next to the ablation zone. Justification of 1-yr follow-up period: HCC recurrence is usually divided in the literature as time-related recurrence: “early” within the two years following the ablation and “late” after two years (reference: Imamura H, et al. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. Journal of hepatology 2003;38:200-207). Early relapse is usually related to tumour features whereas late relapse is related to de novo carcinogenesis. ;Secondary Objective: -To assess the changes of tumorous and non-tumorous perfusion parameters observed with MRI after of neoadjuvant treatment, and before the PA procedure -To assess the Per nodule rates of early response (one month) after a single procedure of PA -To assess the incidences of intra segmental/ extra segmental distant recurrence -To assess the overall survival at 1 and 2 years following PA procedure -To assess the compliance to neoadjuvant and adjuvant treatments -To assess the tolerance of lenvatinib in the setting of neo- and adjuvant therapy to PA ;Primary end point(s): Local recurrence-free survival during a 1-year follow-up after lenvatinib neoadjuvant/adjuvant therapy and PA procedure (see definition above). Recurrence rates (whether local or distant) will be assessed using imaging techniques as recommended by international guidelines (every 3-months US and CT/MRI during one year). Patients who will meet primary endpoint will be alive 1 year after PA procedure without evidence of local recurrence on 3-months MRI evaluations. ;Timepoint(s) of evaluation of this end point: 1 year after PA procedure without evidence of local recurrence on 3-months MRI evaluations. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Changes of tumorous and non-tumorous perfusion parameters observed with MRI after one month of neoadjuvant treatments - Per nodule rates of early response (one month) after a single procedure of PA - Incidences of intra segmental/ extra segmental distant recurrence - Assessment of overall survival at 1 and 2 years following PA procedure: patients will meet this endpoint if they are alive with or without HCC recurrence 1 year, and 2 years after PA procedure. Causes and date of death will be specified when applicable during this timeframe. - Assessment of tolerance of lenvatinib: adverse events related will be monitored according to manufacturer guidelines and recommendation. - Compliance to neoadjuvant and adjuvant treatments - Frequency of SAEs and discontinuations due to AEs ;Timepoint(s) of evaluation of this end point: 1 and 2 years following PA procedure | — |
Countries
France
Contacts
Public ContactSEYMOUR-INAMO
APHP
Outcome results
None listed