Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03071094
Recruitment Status : Active, not recruiting
First Posted : March 6, 2017
Last Update Posted : March 12, 2020
Sponsor:
Information provided by (Responsible Party):
Transgene

Tracking Information
First Submitted Date  ICMJE February 10, 2017
First Posted Date  ICMJE March 6, 2017
Last Update Posted Date March 12, 2020
Actual Study Start Date  ICMJE July 27, 2017
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 28, 2017)
  • 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 ]
    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:
    1. 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.
    2. Any Grade ≥ 3 treatment-related acute immune-related AE involving major organs.
    3. Grade ≥ 3 injection site reaction.
    4. 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.
    5. Any toxicity related to study therapy that results in a delay in treatment of 2 or more weeks.
    6. Neutropenia lasting for more than 7 days; Neutropenic fever; Grade 4 thrombocytopenia or grade 3 thrombocytopenia with clinically significant bleeding.
  • Phase IIa part: To evaluate the anti-tumor activity and efficacy of IT Pexa-Vec combined with IV nivolumab in patients with advanced HCC with respect to Overall Response Rate (ORR) (RECIST 1.1). [ Time Frame: 6 months ]
    Overall response rate (ORR): proportion of patients, whose best overall response is either CR or PR, confirmed at least 4 weeks after initial documentation.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 28, 2017)
  • Disease Control Rate (DCR) at 4 months [ Time Frame: 4 months ]
    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.
  • Overall Survival (OS) [ Time Frame: every 3 months up to 1 year ]
    Proportion of patients alive at specified time points
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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)
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hepatocellular Carcinoma (HCC)
Intervention  ICMJE
  • Biological: Pexastimogene Devacirepvec (Pexa Vec)
    Pexa-Vec (pexastimogene devacirepvec) will be administered as 3 bi-weekly intratumoral (IT) injections of 10^9 pfu at day 1 and weeks 2 and 4
  • Drug: Nivolumab
    Nivolumab will be administered intravenously every 2 weeks (from week 2)
Study Arms  ICMJE Experimental: Pexa-Vec combined with Nivolumab
Interventions:
  • Biological: Pexastimogene Devacirepvec (Pexa Vec)
  • Drug: Nivolumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: February 28, 2017)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2020
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03071094
Other Study ID Numbers  ICMJE TG6006.01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Transgene
Study Sponsor  ICMJE Transgene
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Transgene
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP