Trial of TG4023 Combined With Flucytosine in Liver Tumors

NCT00978107 | Completed Phase 1 DMC

• 2 other identifiers: TG4023.01Eudra CT 2008-005024-90
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 6

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.

Conditions

Hepatocellular Carcinoma

Keywords

Hepatic tumors; Metastatic colorectal cancer

Outcome Measures

Primary Outcomes (1)

• Maximal tolerated dose

  6 months

Secondary Outcomes (1)

• Tumor response of injected and non-injected lesions Viral dissemination Proof of concept: 5-FU concentration in plasma and in tumors

  1 year

Interventions

MVA-FCU1, flucytosine BIOLOGICAL

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.

Also known as: 5-FC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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,

You may not qualify if:

• 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,

Sponsors & Collaborators

• Transgene: lead

Study Sites (6)

Hôpitaux Civils de Colmar

Colmar, 68000, France

Location

Institut Paoli Calmette,

Marseille, 13000, France

Location

Hôpitaux Civils de Lyon,

Pierre-Bénite, 69495, France

Location

Centre René Gauducheau

Saint-Herblain, 44800, France

Location

Hôpitaux Universitaires de Strasbourg

Strasbourg, 67000, France

Location

Institut Claudius Regaud

Toulouse, 31000, France

Location

Related Publications (2)

• Erbs P, Findeli A, Kintz J, Cordier P, Hoffmann C, Geist M, Balloul JM. Modified vaccinia virus Ankara as a vector for suicide gene therapy. Cancer Gene Ther. 2008 Jan;15(1):18-28. doi: 10.1038/sj.cgt.7701098. Epub 2007 Nov 9.

  PMID: 17992203 BACKGROUND

• Husseini F, Delord JP, Fournel-Federico C, Guitton J, Erbs P, Homerin M, Halluard C, Jemming C, Orange C, Limacher JM, Kurtz JE. Vectorized gene therapy of liver tumors: proof-of-concept of TG4023 (MVA-FCU1) in combination with flucytosine. Ann Oncol. 2017 Jan 1;28(1):169-174. doi: 10.1093/annonc/mdw440.

  PMID: 28177438 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Colorectal Neoplasms

Interventions

Flucytosine

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Cytosine; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2009
• First Posted: September 16, 2009
• Study Start: September 1, 2009
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: July 16, 2014

Record last verified: 2014-07

Locations

FR (6)