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Colorectal NeoplasmPhase 1/2NCT03724071

Study of TG6002 (VV TK-RR-FCU1) in Combination With 5-FC in Patients With Advanced Gastro-intestinal Tumors.

A Phase 1/2 study testing TG6002 and Flucytosine (5-FC, Ancotil) in people with Colorectal Neoplasm and Digestive System Neoplasm, run by Transgene at 7 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This study will include two parts: In the phase I part: safety will be assessed in consecutive cohorts of 3 to 6 patients at increasing doses of TG6002 in combination with oral flucytosine (5-FC) in patients with advanced gastro-intestinal (GI) tumors. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
TG6002 and Flucytosine (5-FC, Ancotil)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
51 participants
Where
7 sitesin 3 countries
Study dates
16 Oct 2018to 23 Feb 2023
Phase
Phase 1/2
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

  • Patient population:
  • Phase I part: patients with advanced GI carcinomas having failed and/or intolerant to standard therapeutic options. Patients must have been previously exposed to fluoropyrimidine-based chemotherapy.
  • Phase IIa part: patients with colorectal cancer and liver metastases having failed and/or intolerant to standard therapeutic options. Standard treatment consists of fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, possibly combined with an anti-VEGF and/or an anti-EGFR monoclonal antibody. In addition, the patient should not be candidate to a treatment with regorafenib.
  • Male or female aged ≥18 years.
  • a. Patient presenting with at least one measurable lesion according to RECIST 1.1 in Phase IIa part (optional in the Phase I part) b. Patient presenting with at least one biopsiable metastatic non target lesion (liver metastasis in the Phase IIa part)
  • Expected survival of at least 12 weeks
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  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Absolute neutrophil count (ANC) ≥1000/mm3
  • Blood lymphocyte count ≥500/mm3
  • Hemoglobin (Hb) level ≥10 g/dL
  • Platelet count ≥100,000/mm3
  • Total bilirubin ≤1.5 x Upper Limit of Normal (ULN), except patients with Gilbert syndrome who must have a total bilirubin level of <3.0 x ULN
  • AST, ALT, alkaline phosphatase ≤3 x ULN, unless if liver metastases are present (≤5 x ULN in that case)
  • Clearance for study participation and anti-hypertensive therapy suspension (see exclusion criterion 13) after cardiology consultation and cardiologic investigations including troponin T or I blood level, electrocardiogram (ECG) and cardiac echography (ECHO)
  • Negative blood pregnancy test for women of childbearing potential (WOCBP)
  • Highly effective method of contraception (i.e. methods with a failure rate of less than 1% per year) combined with a barrier method (e.g. condom) for male and female patients during TG6002 treatment period and for a minimum of 3 months following the last administration of TG6002
  • Signed written informed consent in accordance to ICH-GCP and national/local regulation

Who cannot join

  • Previous irradiation of target tumor
  • MSI-High/dMMR colorectal cancer patients
  • Glomerular filtration rate <60 mL/min/1.73m2 according to the Modification of Diet in Renal Diseases (MDRD) formula
  • Immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or immunosuppressant agent, including systemic corticosteroids at a dose >10 mg/day of equivalent prednisolone taken for more than 4 weeks within 3 months prior to TG6002 treatment initiation
  • History of severe exfoliative skin condition (e.g. eczema or atopic dermatitis) requiring systemic therapy for more than 4 weeks within 2 years prior to TG6002 treatment initiation
  • Significant impairment of GI tract absorption, such as total gastrectomy, gastric mucosal atrophy, extensive intestinal resections or malabsorption disease
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  • Symptomatic bacterial intestinal overgrowth consecutive to intestinal dysmotility, surgical resections (blind loops, ileo-cecal valve), or anatomical abnormalities
  • Inflammatory bowel disease (IBD) requiring treatment within the past 2 years prior to TG6002 administration and bowel sub-obstruction
  • Known deficiency in dihydropyrimidine dehydrogenase (DPD)
  • Known hypersensitivity to 5-FC or its excipients
  • Known hypersensitivity to eggs or gentamycin
  • Severe or unstable cardiac disease, including significant coronary artery disease (e.g. requiring angioplasty or stenting) within 12 months prior to TG6002 treatment initiation, unless well-controlled and on stable medical therapy for at least 6 months
  • Inability to withdraw anti-hypertensive therapy 24 hours prior to and up to 24 hours after TG6002 treatment AND/OR patients treated with 3 or more anti-hypertensive agents AND/OR patients with signs of advanced hypertensive disease, such as renal function impairment, left ventricular hypertrophy, hypertensive encephalitis or history of hemorrhagic stroke
  • Patients with other malignancies than the target disease in this trial except cutaneous basal cell carcinoma and in situ carcinoma of the uterine cervix, unless complete remission for at least 5 years prior to study entry and no additional therapy required during the study
  • Systemic anti-cancer therapy or resection surgery within 4 weeks prior to first administration of TG6002
  • Prior participation in another clinical study involving an IMP with last intake within 4 weeks prior to TG6002 treatment initiation
  • Other medical condition or laboratory abnormality that in the judgment of the investigator may increase the risk associated with study participation or may interfere with interpretation of study results
  • Prior gene therapy
  • Concurrent antiviral therapy active on vaccinia viruses (e.g. ribavirin)
  • Nursing (e.g. lactating) females
  • History of severe systemic reaction or side-effect after a smallpox vaccination, such as systemic vaccinia, eczema vaccinatum, encephalitis, myocarditis, pericarditis
  • Any psychological, familiar, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
  • Patient unable or unwilling to comply with the protocol requirements
  • Severe uncontrolled coagulopathy OR anticoagulant medication for therapeutic purposes that cannot be discontinued prior to liver metastasis or other deep-seated tumor biopsies

Trial locations and contacts

7 sites in 3 countries.

7 sites in 3 countries

Spain4 sites

  • Centro Integral Oncológico Clara Campal (CIOCC) Hospital

    Madrid

  • Hospital Universitario 12 de Octubre

    Madrid

  • Instituto de Investigación Sanitaria Fundación Jimenez Díaz

    Madrid

  • Hospital Clinico Universitario

    Valencia

Other trials in Spain

France2 sites

  • Centre Léon Bérard

    Lyon

  • IUCT Toulouse

    Toulouse, 31100

Other trials in France

Belgium1 site

  • Institut Jules Bordet

    Brussels

Other trials in Belgium

About this study

Official title: A Phase I/IIa Study of TG6002 (VV TK-RR-FCU1) Administered by Intravenous (IV) Infusions in Combination With Oral Flucytosine (5-FC) in Patients With Advanced Gastro-intestinal (GI) Tumors.

This study will include two parts:

  • In the phase I part: safety will be assessed in consecutive cohorts of 3 to 6 patients at increasing doses of TG6002 in combination with oral flucytosine (5-FC) in patients with advanced gastro-intestinal (GI) tumors.
  • In the phase IIa part: evaluation of efficacy and further evaluation of safety of multiple administrations of TG6002 in combination with flucytosine (5-FC) in patients with colorectal cancer and liver metastases.

In both parts, tumor response will be evaluated on local assessment using RECIST 1.1.

All patients will be followed up until disease progression or death due to any cause or the date of data cut-off, whichever occurs first.

Being tested
TG6002, Flucytosine (5-FC, Ancotil)
Medical subject headings
Colorectal Neoplasms, Digestive System Neoplasms

What participants receive

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

  • TG6002Biological

    Phase I, Arm A: Dose escalation from 1 x 10E6 PFU to 1 x 10E9 PFU; Phase I, Arm B: Dose escalation from 1 x 10E9 PFU to 1 x 10E10 PFU; Phase II: Established recommended Phase II dose (RP2D)

    Administration intravenously on Days 1, 8 and 15 (Phase I, Arm A) or on Days 1, 3 and 5 (Phase I, Arm B). Three intravenous infusions at the Dose Recommended for Phase 2 (RP2D) in Phase IIa.

    An extension of the 28-day cycle of TG6002/5-FC combination can be repeated in case of evidence of patient benefit, defined as an objective radiological response or disease stabilization, and/or a clinically significant relief in patient's symptoms. Additional cycle(s) will start from 2 to 4 weeks following the last 5-FC intake.

  • Flucytosine (5-FC, Ancotil)Drug

    Administered orally at a dose of 200 mg/kg/day for a total of 10 days (Phase I, Arm B) or 16 days (Phase I, Arm A).

    An extension of the cycle of TG6002/5-FC combination can be repeated in case of evidence of patient benefit, defined as an objective radiological response or disease stabilization, and/or a clinically significant relief in patient's symptoms.

Study groups in NCT03724071
Study groupRoleWhat they receive
Phase 1, Arm A - Dose escalation and safety of TG6002 and flucytosine combinationExperimentalDose escalation with repeated administrations of TG6002 in combination with flucytosine in patients with advanced gastro-intestinal (GI) tumors.
Receives: Biological: TG6002; Drug: Flucytosine (5-FC, Ancotil)
Phase 1, Arm B - Dose escalation and safety of TG6002 and flucytosine combinationExperimentalDose escalation with closer administrations of TG6002 in combination with flucytosine in patients with advanced gastro-intestinal (GI) tumors.
Receives: Biological: TG6002; Drug: Flucytosine (5-FC, Ancotil)
Phase IIa - Efficacy of TG6002 and flucytosine combinationExperimentalRepeated administrations of TG6002 in combination with flucytosine in patients with colorectal cancer and liver metastases
Receives: Biological: TG6002; Drug: Flucytosine (5-FC, Ancotil)

What is being measured

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

  1. Phase I part - Dose-limiting toxicities

    Dose-limiting toxicities

    Measured: Day 28

  2. Phase II part - Overall response rate

    Overall response rate according to Recist v1.1

    Measured: Day 43

Timeline

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

  1. First posted30 Oct 2018
  2. Study start16 Oct 2018
  3. Primary completion23 Feb 2023
  4. Study completion23 Feb 2023

Why it stopped: Study has been terminated after Phase I part on 23 February 2023

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
51 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03724071
Sponsor's protocol ID
TG6002.02
Status last verified
Jun 2023
First submitted
16 Oct 2018
Last updated
23 Jun 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing TG6002 and Flucytosine (5-FC, Ancotil) in people with Colorectal Neoplasm and Digestive System Neoplasm, run by Transgene at 7 sites in 3 countries.

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 17 inclusion and 24 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: stopped early, as of the sponsor's last update on 23 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Spain, France, Belgium. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 was stopped early (reason given: Study has been terminated after Phase I part on 23 February 2023). Results are not available in the source record.

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?

Phase I part - Dose-limiting toxicities (time frame: Day 28). The study lists 2 primary outcomes in all. 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 NCT03724071.

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 23 Jun 2023.

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