Hepatocellular Carcinoma
Conditions
Keywords
Hepatic tumors, Metastatic colorectal cancer
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.
Interventions
BIOLOGICALMVA-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.
Sponsors
Transgene
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximal tolerated dose | 6 months |
Secondary
| Measure | Time frame |
|---|---|
| Tumor response of injected and non-injected lesions Viral dissemination Proof of concept: 5-FU concentration in plasma and in tumors | 1 year |
Countries
France
Outcome results
None listed