Clinical trial NCT03071094: A Trial to Evaluate the Safety and Efficacy of the Combination of the Oncolytic Immunotherapy Pexa-Vec With the PD-1 Receptor Blocking Antibody Nivolumab in the First-line Treatment of Advanced Hepatocellular Carcinoma (HCC)
Official title: A Phase I/IIa Trial to Evaluate the Safety and Efficacy of the Combination of the Oncolytic Immunotherapy Pexa-Vec With the PD-1 Receptor Blocking Antibody Nivolumab in the First-line Treatment of Advanced Hepatocellular Carcinoma (HCC)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Hepatocellular Carcinoma (HCC)
Lead sponsor: Transgene
Sponsor class: INDUSTRY
First posted: 2017-03-06
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a study to Evaluate the Safety and Efficacy of the Combination of the Oncolytic Immunotherapy Pexa-Vec With the PD-1 Receptor Blocking Antibody Nivolumab in the First-line Treatment of Advanced Hepatocellular Carcinoma (HCC).


Eligibility criteria: Inclusion Criteria:

* Histological/cytological diagnosis of primary HCC, excluding cholangiocarcinoma, hepatocholangiocarcinoma, fibrolamellar carcinoma and hepatoblastoma
* Advanced stage HCC per EASL-EORTC (European Association for the Study of the Liver-European Organisation for Research and Treatment of Cancer) guidelines, i.e. patients who are not candidates for curative interventions and not candidates for locoregional modalities
* Patients naïve to systemic therapy for HCC
* Tumor status (as determined by radiology evaluation): At least one measurable viable tumor in the liver, ≥1 cm longest diameter (LD), using a dynamic imaging technique (arterial phase of triphasic computerized tomography \[CT\] scan, or dynamic contrast-enhanced magnetic resonance imaging \[MRI\]), and injectable under imaging-guidance (CT or ultrasound)
* At least one tumor that has not received prior local-regional treatment, or that has exhibited definitive growth of viable tumor since prior local-regional treatment of HCC undertaken at least 4 weeks prior to enrolment or 3 months prior to enrolment for radioembolization
* Child-Pugh Class A. Note: paracentesis, albumin infusion or diuretic treatment cannot be used to downgrade Child-Pugh score (e.g., to improve from severe to moderate/mild or from moderate to mild ascites)
* Performance status 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
* Adequate hematological, hepatic, and renal function
* Additional inclusion criteria exist

Exclusion Criteria:

* Histological diagnosis of cholangiocarcinoma, hepatocholangiocarcinoma, fibrolamellar carcinoma and hepatoblastoma
* Symptomatic cardiovascular disease, including but not limited to significant coronary artery disease (e.g., requiring angioplasty or stenting) or congestive heart failure within the preceding 12 months
* Current or past history of cardiovascular disease (e.g., past history of myocardial infarction, ischemic cardiomyopathy) unless cardiology consultation and clearance has been obtained for study participation
* History of moderate or severe ascites, bleeding esophageal varices, hepatic encephalopathy or pleural effusions related to liver insufficiency within 6 months of screening; patients with adequately treated esophageal varices are allowed
* Active, known or suspected significant immunodeficiency due to underlying illness including HIV/AIDS, autoimmune diseases, and/or immune-suppressive medication including high-dose corticosteroids
* History of severe eczema and/or ongoing severe inflammatory skin condition (as determined by the Investigator) requiring medical treatment
* Any known allergy or reaction to any component of nivolumab formulation or its excipients
* Additional exclusion criteria exist

Primary outcomes:
measure: Phase I: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: 4 weeks from the first study drug administration
measure: Phase I: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: 4 weeks from the first study drug administration
measure: Overall Response Rate (ORR) According to RECIST 1.1.
timeFrame: 6 months from the first study drug administration
Secondary outcomes:
Other outcomes:
Locations:
city: Nancy
country: France
facility: Site No 0102
city: Paris
country: France
facility: Site No 0101
Study officials:
References: