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Hepatocellular CarcinomaPhase 1NCT00978107

Trial of TG4023 Combined With Flucytosine in Liver Tumors

A Phase 1 study testing MVA-FCU1, flucytosine in people with Hepatocellular Carcinoma, run by Transgene at 6 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatocellular Carcinoma
What is being tested?
MVA-FCU1, flucytosine
How many people
16 participants
Where
6 sitesFrance
Study dates
Sep 2009to Sep 2011
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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,
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  • 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.

Who cannot join

  • 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,
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  • 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,

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

France6 sites

  • Hôpitaux Civils de Colmar

    Colmar, 68000

  • Institut Paoli Calmette,

    Marseille, 13000

  • Hôpitaux Civils de Lyon,

    Pierre-Bénite, 69495

  • Centre René Gauducheau

    Saint-Herblain, 44800

  • Hôpitaux Universitaires de Strasbourg

    Strasbourg, 67000

  • Institut Claudius Regaud

    Toulouse, 31000

Other trials in France

About this study

Official 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.

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.

Being tested
MVA-FCU1, flucytosine
Keywords
Hepatic tumors, Metastatic colorectal cancer
Medical subject headings
Carcinoma, Hepatocellular, Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MVA-FCU1, flucytosineBiological

    Also called 5-FC

    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)
    1. 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.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximal tolerated dose

    Measured: 6 months

Secondary outcomes (1)

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

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Sep 2009 (estimated)
  2. Study startSep 2009
  3. Primary completionSep 2011
  4. Study completionSep 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00978107
Sponsor's protocol ID
TG4023.01
Other IDs
Eudra CT 2008-005024-90
Status last verified
Jul 2014
First submitted
15 Sep 2009
Last updated
16 Jul 2014
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 17992203

  • 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.

    PubMed 28177438

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MVA-FCU1, flucytosine in people with Hepatocellular Carcinoma, run by Transgene at 6 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximal tolerated dose (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00978107, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2014.

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