Etude : HELP /

ATTENTION : pour chaque essai clinique, les éléments affichés ci-dessous ne sont pas exhaustifs, et le protocole fourni par le promoteur reste l’unique document à consulter pour mener à bien un essai clinique sur centre. Pour plus d'informations, contactez le référent du territoire concerné.

Type d'étude
Présentation de l'étude
Acronyme : HELP

Nom :

Traitement : Métastatique ou localement avancé

Type d'étude : Hors ciblage moléculaire

Dernière MÀJ : 28/01/2020
CIM10 - Localisation(s)
Informations principales
Titre : Analysis of cfDNA in Patients With Hepatocarcinoma and Treated by Sorafenib or Regorafenib

Spécialité : Organes digestifs
Localisation : C22 - Tumeur maligne du foie et des voies biliaires intrahépatiques
Informations complémentaires
Schéma : The aim of this trial is to investigate whether quantitative analysis of the total concentration of circulating free deoxyribonucleic acid (cfDNA) and of the cfDNA integrity index (DII) (Intplex®) may reflect hepatocellular carcinoma (HCC) tumor dynamics or response for patients treated by Sorafenib or Regorafenib and if it could be used as a tool for patient management under targeted therapy.

study design:
Blood sample at baseline, 15 days, 4-8-16 weeks and then every 12 weeks
In vitro diagnostic device: Intplex test

Current primary outcome:
Detection rate of total circulating free deoxyribonucleic acid (cfDNA) concentration at the baseline. [ Time Frame: Baseline ]
Total cfDNA concentration is considered as detected if total cfDNA concentration ≥ 5 ng/mL and not detected if total cfDNA concentration < 5 ng/mL

Current secondary outcomes:
- total circulating free deoxyribonucleic acid (cfDNA) fragmentation index [ Time Frame: Baseline ]
Fragmentation of cfDNA
- Objective response rate [ Time Frame: Approximately 36 months ]
From the date of inclusion to the date of death from any cause
- Disease control rate [ Time Frame: Approximately 36 months ]
From the date of inclusion to the date of death from any cause
- Progression-Free Survival [ Time Frame: Approximately 36 months ]
The time from the date of start of Sorafenib (Regorafenib respectively) to the date of first documented
- Time-to-progression [ Time Frame: Approximately 36 months ]
The time from the date of start of Sorafenib (Regorafenib respectively) to the date of first documented progression ( radiological or clinical)
- Overall Survival [ Time Frame: Approximately 36 months ]
The time from the date of start of Sorafenib to the date of documented death from any cause

Phase : NA

Stade : Localement avancé à Métastasique

1, 2, 3, 4, X
Informations libres de droit
Critères d'inclusion
Critères de non-inclusion
Informations libres de droit
Critères d'inclusion et de non-inclusion
Critères d'inclusion : - Male or female patients ≥ 18 years of age
- Histological or cytological documentation of hepatocellular carcinoma (HCC) or non-invasive diagnosis of HCC as per American Association for the Study of Liver Diseases (AASLD) criteria in patients with a confirmed diagnosis of cirrhosis
- Barcelona Clinical Liver Cancer (BCLC) stage Category B or C that cannot benefit from local treatments such as resection, local ablation, chemoembolization
- At least one uni-dimensional measurable lesion by computed tomography (CT) scan or magnetic resonance imaging (MRI) according to RECIST criteria 1.1 and modified RECIST for HCC
- 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:
Hemoglobin > 8.5 g/dL
Absolute neutrophil count ≥ 1500/mm3
Platelet count ≥ 60,000/ mm3
Total bilirubin ≤ 2 mg/dL
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x upper limit of normal (ULN)
Serum creatinine ≤ 1.5 x Upper limit normal (ULN)
Lipase ≤ 2 x ULN
Prothrombin time-international normalized ratio (PT-INR) < 2.3 x ULN and partial thromboplastin time (PTT) < 1.5 x ULN
Glomerular Filtration Rate (GFR) ≥ 30 mL/min/1.73 m2
- Life expectancy ≥ 3 months
- Women of childbearing potential and men must agree to use adequate contraception
- Patients must be affiliated to a Social Security System
- Written informed consent signed
- Patients initially treated with Sorafenib, will be switched to Regorafenib if all the above conditions are still met and, in addition:
- Documented progression under treatment with Sorafenib (defined as documented radiological and/or clinical and/or biological progression)

Critères de non-inclusion : - Prior liver transplantation or candidates for liver transplantation
- Hypersensitivity to the active substance or to any of the excipients
- Patients with large esophageal 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 tumors. Any cancer curatively treated > 3 years prior to study entry is permitted
- Known history or symptomatic metastatic brain or meningeal tumors
- Major surgical procedure or significant traumatic injury within 28 days before enrollment
- Congestive heart failure New York Heart Association (NYHA) ≥ class 2
- Unstable angina or myocardial infarction within the past 6 months before enrollment
- Cardiac arrhythmias requiring anti-arrhythmic therapy
- Uncontrolled hypertension
- Patients with phaeochromocytoma
- Uncontrolled ascites
- 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 required
- Clinically significant bleeding NCI-CTCAE version 4.0 ≥ Grade 3 within 30 days before enrollment
- Arterial or venous thrombotic or embolic events such as cerebrovascular accident, deep vein thrombosis or pulmonary embolism within 6 months before enrollment
- 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
- Known history of human immunodeficiency virus (HIV) infection
- Seizure disorder requiring medication
- Non-healing wound, ulcer or bone fracture
- Active autoimmune disease (lupus, sclerodermia, rheumatoid arthritis, …)
- Any malabsorption condition
- Breast feeding
- Pregnancy
- High performance sport practice
- Patient unable to swallow oral medication
- Patients who discontinue sorafenib will not be switched to regorafenib if any of the condition listed above occurs and/or the following criteria are met:
- Prior discontinuation of prior Sorafenib therapy due to Sorafenib-related toxicity - Unresolved toxicity (Sorafenib) ≥ NCI-CTCAE version 4.0 Grade 2
Informations relatives au promoteur
Promoteur :
Institut du Cancer de Montpellier - Val d'Aurelle
Type de sponsor : Institutionnel
Institut du Cancer de Montpellier - Val d'Aurelle

Coordonnateur :
Docteur Jean-Pierre BLEUSE
Centre investigateur
Informations relatives aux investigateurs
Centre investigateur :
Centre Hospitalier Universitaire de Lille - 2 Avenue Oscar Lambret - 59000 LILLE

Investigateur :
Professeur Philippe MATHURIN

Daphnée SORET
03 20 44 59 62 - Poste 30671

Statut de l'essai : OUVERT

MAJ : 13/01/2020