Nivolumab in neoadjuvant and adjuvant setting in patients with advanced HCC treated by electroporation MedDRA version: 20.0 Level: PT Classification code 10073071 Term: Hepatocellular carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Opdivo
Product Name: Opdivo
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Nivolumab
CAS Number: 946414-94-4
Other descriptive name: anti- PD1 monoclonal antibody
Concentr
Sponsors
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Male or female patients superior or equal 18 years - Histological or cytological documentation of 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 - Patients with HCC amenable for EP as assessed by multidisciplinary board corresponding to the following extension: o Uninodular HCC >3cm and 8.5 g/dL o Absolute neutrophil count superior or equal 1500/mm3 o Platelet count superior or equal 60,000/ mm3 o Total bilirubin inferior or equal 2 mg/dL o Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) inferior or equal 5 x upper limit of normal (ULN) o Serum creatinine inferiror or equal 1.5 x ULN o Lipase inferiro or equal 2 x ULN o Prothrombine time-international normalized ratio (PT-INR) =65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
Exclusion criteria: Patients with past history of HCC - Patients with contraindications to EP - 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 - Patients with autoimmune disease and patients requiring chronic systemic treatment with corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications. - 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 enrolment - Congestive heart failure New York Heart Association superior or equal class 2 - Unstable angina or myocardial infarction within the past 6 months before enrolment - Cardiac arrhythmias requiring anti-arrhythmic therapy - Grade 3 (severe) hypertension superior or equal 180 and/or superior or equal 110 mmHG (systolic and diastolic, according to National Heart Foundation 2016) - 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 superior or equal 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 superior or equal Grade 3 within 30 days before enrolment - Arterial or venous thrombotic or embolic events such as cerebrovascular accident, deep vein thrombosis or pulmonary embolism within 6 months 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 - Known history of human immunodeficiency virus (HIV) infection - Seizure disorder requiring medication - 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 2-years follow-up after Nivolumab neoadjuvant/adjuvant therapy and EP procedure.;Secondary Objective: -To assess the changes of tumorous and non-tumorous perfusion parameters observed with CUS and MRI after one months of neoadjuvant treatments -To assess the Per nodule rates of early response (one month) after a single procedure of EP -To assess the incidences of intra segmental/ extra segmental distant recurrence -To assess the overall survival at 2-yrs following EP procedure -To assess the compliance to neoadjuvant and adjuvant treatments -To assess the tolerance of Nivolumab in the setting of neo- and adjuvant therapy to EP -Tumoral and non tumoral assessment (histological and molecular study) of the effect of nivolumab at 1 month: tumor apoptosis and lymphocyte infiltration, expression of immunity modulating genes -Peripheral blood approach of the effect of immunotherapy: changes in phenotypic and functional characteristic of circulating lymphocytes subpopulation, cytokine, chemokine and metabolomic profile changes under therapy ;Primary end point(s): Efficacy endpoint is remission of treated nodules. At M1 post EP, a tumor will be considered completely ablated if no nodular or irregular enhancement is visible next to the ablation zone during the arterial phase, with washout within the portal phase. After the ablation will be considered complete, local tumor progression will be defined as the emergence of irregular areas enhanced at the arterial phase followed by washout at the portal phase next to the ablation zone. Local tumor progression will also include cases of failure of initial IRE treatment course, reported per nodule. As a consequence: 1- Primary endpoint is achieved if a given patient is alive without local recurrence as defined in the above criteria 2- All secondary endpoints will be assessed as defined in the above criteria | — |
Countries
France
Contacts
Public ContactDRCI Hôpital St Louis
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
Outcome results
None listed