Trial of TG4023 Combined With Flucytosine in Liver Tumors

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,