E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with a non resectable HCC registered on national waiting list for LT with no complete response to TACE as a bridging loco-regional treatment. |
NA |
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E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019828 |
E.1.2 | Term | Hepatocellular carcinoma non-resectable |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To estimate the proportion of LT among patients under lenvatinib with no complete response after 2 TACE. |
ND |
|
E.2.2 | Secondary objectives of the trial |
- To estimate time to progression under lenvatinib and until LT - To compare progression rate under lenvatinib and until LT with the theorical proportion of 20%. - To estimate the response rate by imaging before LT - To estimate the response rate by liver specimen pathology after LT - To estimate the recurrence rate after LT - To demonstrate the safety of this sequential strategy - Characterization of immune cell population of peripheral change under treatment. |
ND |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patient presenting with - Non resectable HCC - Initial French AFP score < or = 2 - Registered on national waiting list for LT - Who underwent TACE as a bridge to LT - With no complete response after 2 TACE (i.e. persistent active disease, including stable disease or partial response or progression) - Non eligible for percutaneous ablation - Informed, written consent obtained from the patient - Having the rights to French social insurance - Aged of 18 years or older - Adequate bone marrow, liver and renal function as assessed by the following laboratory tests: * Hemoglobin > 8.5 g/dL * Absolute neutrophil count ≥ 1500/mm3 (≥ 1200/mm3 for black/African, American) * Platelet count ≥ 60,000/ mm3 * Total bilirubin ≤ 2 mg/dL or 34 mcmol/l * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x upper limit of normal (ULN) * Serum creatinine ≤ 1.5 x ULN * Prothrombine time-international normalized ratio (PT-INR) < 2.3 and PTT < 50 % * Glomerular Filtration Rate (GFR) ≥ 30 mL/min/1.73 m2 - 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.
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ND |
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E.4 | Principal exclusion criteria |
- Contraindication of lenvatinib and excipient 1- Cardiovascular: * Rhythmic or ischemic recent or uncontrolled cardiac disease: Pacemakers or patients who have a history of cardiac arrhythmias or irregular heartbeats (in case of electroporation procedure) * Congestive heart failure New York Heart Association (NYHA) ≥ class 2 * Unstable angina or myocardial infarction within the past 6 months before enrolment * Uncontrolled arterial hypertension (systolic ≥ 140 mmHg, diastolic ≥ 90 mmHg) 2- Ongoing ascites: 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) 3- Coagulopathy 4- Ongoing infection > Grade 2 according to NCI-current CTCAE . Hepatitis B is allowed if no active replication is present (below 100 IU/mL). Hepatitis C is allowed if no antiviral treatment is ongoing - Known hypersensitivity to the study drug or excipients in the formulation - Decompensated cirrhosis (Child-Pugh > A6) - Prior systemic therapy with oral TKI and/or immunotherapy - 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 - Recent digestive bleeding associated with portal hypertension (whithin the 3 months prior to inclusion in the study) - Advanced or Metastatic HCC (BCLC C) - Persistent proteinuria of NCI-current CTCAE ≥ Grade ≥ Grade 3 - Project of living donor - Pregnant or lactating woman - Curator or guardianship or patient placed under judicial protection - Participation in other interventional research during the study . |
ND |
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E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of patients with TACE failure and treated with lenvatinib who have a LT. |
ND |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Time to progression under lenvatinib before LT by imaging. Progression will be based on RECIST and mRECIST. - Progression under lenvatinib before LT by imaging. Progression will be based on RECIST and mRECIST. - Response rate before LT by imaging - Response rate by liver specimen pathology after the LT - Recurrence rate after LT by imaging - Evaluate Safety by AE and SAE (using current CTCAE ) The endpoints associated to the immunophenotyping of peripheral blood immune cell population will be on the ancillary analyses. |
ND |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- within 12 months of treatment for imaging and safety and immunophenotyping - at the time of transplantation for histological characterization - within 18 months after LT for imaging recurrence. |
ND |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |