Trial of TG4023 Combined With Flucytosine in Liver Tumors

Phase 1

Completed

• Conditions: Hepatocellular Carcinoma

• Registration Number: NCT00978107
• Lead Sponsor: Transgene

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2009-09
• Study First Submitted: 2009-09-15
• Study First Submitted QC: 2009-09-15
• Study First Posted: 2009-09-16
• Primary Completion: 2011-09
• Study Completion: 2011-09
• Status Verified: 2014-07
• Last Update Submitted: 2014-07-15
• Last Update Posted: 2014-07-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

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,

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Maximal tolerated dose	6 months

Secondary Outcome Measures

Name	Time	Method
Tumor response of injected and non-injected lesions Viral dissemination Proof of concept: 5-FU concentration in plasma and in tumors	1 year

Trial Locations

Locations (6)

Hôpitaux Civils de Colmar; 🇫🇷 Colmar, France

Institut Paoli Calmette,; 🇫🇷 Marseille, France

Hôpitaux Civils de Lyon,; 🇫🇷 Pierre Benite, France

Centre René Gauducheau; 🇫🇷 Saint Herblain, France

Hôpitaux Universitaires de Strasbourg; 🇫🇷 Strasbourg, France

Institut Claudius Regaud; 🇫🇷 Toulouse, France