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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)

NCT03071094

Description:

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).

Related Conditions:
  • Hepatocellular Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: TG6006.01
  • NCT ID: NCT03071094

Conditions

  • Hepatocellular Carcinoma (HCC)

Interventions

DrugSynonymsArms
Pexastimogene Devacirepvec (Pexa Vec)Pexa-Vec combined with Nivolumab
NivolumabPexa-Vec combined with Nivolumab

Purpose

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).

Trial Arms

NameTypeDescriptionInterventions
Pexa-Vec combined with NivolumabExperimental
  • Pexastimogene Devacirepvec (Pexa Vec)
  • Nivolumab

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase I part: To evaluate the safety profile of intratumoral (IT) Pexa-Vec combined with intravenous (IV) nivolumab in patients with advanced HCC. Dose Limiting Toxicities (DLTs)
Time Frame:4 weeks
Safety Issue:
Description:DLTs are defined as the occurrence of any of the following events evaluated as related to study drugs and occurring during the first 4 weeks: All Grade 3-4 non-hematologic toxicity that represent a 2-grade increase over baseline, excluding: inadequately treated nausea, vomiting and diarrhea, alopecia, transient fatigue and laboratory/metabolic abnormalities. Any Grade ≥ 3 treatment-related acute immune-related AE involving major organs. Grade ≥ 3 injection site reaction. AST or ALT ≥ 10xULN, unless it is related to a definite progression of liver metastases or another clearly identifiable etiology; doubling of AST or ALT that is concurrent with a doubling of the total bilirubin. Any toxicity related to study therapy that results in a delay in treatment of 2 or more weeks. Neutropenia lasting for more than 7 days; Neutropenic fever; Grade 4 thrombocytopenia or grade 3 thrombocytopenia with clinically significant bleeding.

Secondary Outcome Measures

Measure:Disease Control Rate (DCR) at 4 months
Time Frame:4 months
Safety Issue:
Description:4-month DCR: proportion of patients whose best overall response in the study is either CR, PR, or stable disease (SD) 4 months after D1.
Measure:Overall Survival (OS)
Time Frame:every 3 months up to 1 year
Safety Issue:
Description:Proportion of patients alive at specified time points

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Transgene

Last Updated

March 11, 2020