Trial of TG4023 Combined With Flucytosine in Liver Tumors

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00978107
• Date of registration: 15/09/2009
• Prospective Registration: No
• Primary sponsor: Transgene
• Public title: Trial of TG4023 Combined With Flucytosine in Liver Tumors
• Scientific 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.
• Date of first enrolment: September 2009
• Target sample size: 16
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00978107
• Study type: Interventional
• Study design: Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 1

Countries of recruitment

France

Key inclusion & exclusion 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,



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Hepatocellular Carcinoma

Intervention(s)

Biological: MVA-FCU1, flucytosine

Primary Outcome(s)

Maximal tolerated dose [Time Frame: 6 months]

Secondary Outcome(s)

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]

Secondary ID(s)

TG4023.01

Eudra CT 2008-005024-90

Source(s) of Monetary Support

Please refer to primary and secondary sponsors