Immunotherapy in neoadjuvant and adjuvant setting in patients with advanced HCC treated by electroporation in curative intent: French multicenter phase 2 therapeutic trial - NIVOLEP

Phase 1

• Conditions: ivolumab in neoadjuvant and adjuvant setting in patients with advanced HCC treated by electroporation; MedDRA version: 20.0Level: PTClassification code 10073071Term: Hepatocellular carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-004679-29-FR
• Lead Sponsor: ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-04-17
• Last Update Posted: 7 January 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 50

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:
oUninodular HCC >3cm and <5cm
oMultinodular HCC
-At least one uni-dimensional measurable lesion by computed tomography (CT) scan or magnetic resonance imaging (MRI) according to modified RECIST for HCC
-Liver function status Child-Pugh Class A
-Eastern Cooperative Oncology Group (ECOG) Performance Status inferior or equal 2
-Adequate bone marrow, liver and renal function as assessed by the following laboratory tests:
oHemoglobin > 8.5 g/dL
oAbsolute neutrophil count superior or equal 1500/mm3
oPlatelet count superior or equal 60,000/ mm3
oTotal bilirubin inferior or equal 2 mg/dL
oAlanine aminotransferase (ALT) and aspartate aminotransferase (AST) inferior or equal 5 x upper limit of normal (ULN)
oSerum creatinine inferiror or equal 1.5 x ULN
oLipase inferiro or equal 2 x ULN
oProthrombine time-international normalized ratio (PT-INR) < 2.3 x ULN and PTT < 1.5 x ULN
oGlomerular Filtration Rate (GFR) superior or equal 30 mL/min/1.73 m2
-Life expectancy superior or equal 3 months
-Women of childbearing potential (WOCBP) need to accept one effective method of contraception until 5 months after the last nivolumab infusion
- Men who are sexually active with WOCBP partners need to accept one effective method of contraceptionuntil 7 months after the nivolumab infusion
and men must agree to use adequate contraception
-Patients affiliated to a Social Security System
-Written informed consent signed

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 25
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 25

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified