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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)

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ClinicalTrials.gov Identifier: NCT03071094
Recruitment Status : Recruiting
First Posted : March 6, 2017
Last Update Posted : June 6, 2018
Sponsor:
Information provided by (Responsible Party):
Transgene

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).

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma (HCC) Biological: Pexastimogene Devacirepvec (Pexa Vec) Drug: Nivolumab Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : July 27, 2017
Estimated Primary Completion Date : April 2019
Estimated Study Completion Date : October 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Arm Intervention/treatment
Experimental: Pexa-Vec combined with Nivolumab 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)




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. Overall Survival (OS) [ Time Frame: every 3 months up to 1 year ]
    Proportion of patients alive at specified time points



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03071094


Contacts
Contact: Transgene EU Clinical Operations Department + 33 (0) 3 88 27 91 00 clinical.trials@transgene.fr

Locations
France
Site No 0102 Recruiting
Nancy, France
Site No 0101 Recruiting
Paris, France
Sponsors and Collaborators
Transgene

Responsible Party: Transgene
ClinicalTrials.gov Identifier: NCT03071094     History of Changes
Other Study ID Numbers: TG6006.01
First Posted: March 6, 2017    Key Record Dates
Last Update Posted: June 6, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Antibodies
Antibodies, Monoclonal
Antibodies, Blocking
Nivolumab
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents