Trial of TG4023 Combined With Flucytosine in Liver Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Transgene
ClinicalTrials.gov Identifier:
NCT00978107
First received: September 15, 2009
Last updated: July 15, 2014
Last verified: July 2014
  Purpose

This trial is a phase I, open-label, dose-escalating study of the safety or percutaneous intra-tumoral injection of TG4023 (MVA-FCU1) combined with systemic administration of 5-fluorocytosine in patients with primary or secondary hepatic tumors.


Condition Intervention Phase
Hepatocellular Carcinoma
Biological: MVA-FCU1, flucytosine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I, Open-label, Dose-escalating Study of the Safety or Percutaneous Intra-tumoral Injection of TG4023 (MVA-FCU1) Combined With Systemic Administration of 5-fluorocytosine in Patients With Primary or Secondary Hepatic Tumors.

Resource links provided by NLM:


Further study details as provided by Transgene:

Primary Outcome Measures:
  • Maximal tolerated dose [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Tumor response of injected and non-injected lesions Viral dissemination Proof of concept: 5-FU concentration in plasma and in tumors [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Enrollment: 16
Study Start Date: September 2009
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: MVA-FCU1, flucytosine
    1. TG4023: single IT injection; possibility to re-administer once,

      • Percutaneous IT injections, under radiological or ultrasound imaging guidance
      • Dose-escalating schedule of administration: 107 pfu (Cohort #1), 108 pfu (Cohort #2) and 4x108 pfu (Cohort #3),
      • MTD injected to up to 3 different lesions (Cohort #4)
    2. 5-FC (5-fluorocytosine)/flucytosine

      • Dose and dosing schedule:

        • Daily starting dose of 200 mg/kg; daily dose will be adjusted after measurement of 5-FC plasma concentration at steady state, which should be kept below 100 mg/L
        • Duration: 2 weeks.
      • Possible routes of administration:

        • PO: 500 mg tablets, qid
        • IV: 1% 250 mL vials, 45-minute infusions.
    Other Name: 5-FC
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with advanced disease without any other standard of care treatment options:

    • hepatic metastases of colorectal cancer (CRC) or of other cancers
    • Hepatocellular carcinoma (HCC)
  • At least one unresectable target tumor located in the liver, measuring 2-5 cm and accessible to IT administration of TG4023 and amenable to radiological measurement using RECIST,
  • Weight ≤ 100 kg,
  • Patients with stable disease, who have to discontinue chemotherapy because of intolerance,
  • ECOG performance status ≤ 2,
  • Life expectancy ≥ 3 months,
  • Hematology:

    • Absolute neutrophil count > 1,500/mm3,
    • Hemoglobin > 9g/dL,
    • Platelet count > 100,000/mm3,
    • Prothrombin time international normalized ratio (INR) ≤ 2; partial thromboplastin time ≤ 1.66 times upper limit of normal (ULN),
  • Biochemistry:

    • Total bilirubin ≤ 3 x ULN,
    • Aspartate amino-transferase (AST), alanine amino-transferase (ALT), alkaline phosphatase

      • 5.0 x ULN,
    • Creatinin clearance ≥ 40 mL/min,
    • Total albumin ≥ 30 g/L,
  • Anti-vitamin K anticoagulants should have been switched for low-molecular weight heparin prior to TG4023 injection,
  • Signed, written Independent Ethics Committee (IEC)-approved informed consent.

Exclusion Criteria:

  • Child-Pugh stage C hepatic insufficiency,
  • Impaired renal function (creatinin clearance < 40 mL/min),
  • Known deficiency in dihydropyrimidine dehydrogenase (DPD) or total DPD deficiency diagnosed at baseline in those patients not previously treated with 5-FU-related compounds,
  • Ascites,
  • Brain metastases,
  • Significant impairment of gastro-intestinal (GI) tract absorption capacity, such as total gastrectomy, gastric mucosal atrophy, extensive intestinal resections or malabsorption disease will not be treated by oral 5-FC,
  • History of bleeding disorders,
  • Pregnant or breast-feeding women,
  • Human Immunodeficiency Virus (HIV) positive,
  • Chronic use of immunodepressants within 4 weeks prior to TG4023 injection or immune-depressed patients,
  • Hypersensitivity to 5-FC,
  • Hypersensitivity to egg proteins,
  • Concomitant or previous chemotherapy or targeted therapy within 4 weeks prior to TG4023 injection and last treatment with bevacizumab (Avastin®) within 2 months prior to TG4023 injection,
  • Concomitant treatment with anti-inflammatory drugs: systemic cortico-steroids and non-steroidal anti-inflammatory drugs (NSAIDs),
  • Prior gene therapy,
  • Prior participation in any other research protocol involving an IMP within 2 months prior to TG4023 injection,
  • Major surgery within 6 weeks of TG4023 injection,
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00978107

Locations
France
Hôpitaux Civils de Colmar
Colmar, France, 68000
Institut Paoli Calmette,
Marseille, France, 13000
Hôpitaux Civils de Lyon,
Pierre Benite, France, 69495
Centre René Gauducheau
Saint Herblain, France, 44800
Hôpitaux Universitaires de Strasbourg
Strasbourg, France, 67000
Institut Claudius Regaud
Toulouse, France, 31000
Sponsors and Collaborators
Transgene
  More Information

Publications:
Responsible Party: Transgene
ClinicalTrials.gov Identifier: NCT00978107     History of Changes
Other Study ID Numbers: TG4023.01, Eudra CT 2008-005024-90
Study First Received: September 15, 2009
Last Updated: July 15, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Transgene:
Hepatic tumors
Metastatic colorectal cancer

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
Flucytosine
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014