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

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ClinicalTrials.gov Identifier: NCT03724071
Recruitment Status : Recruiting
First Posted : October 30, 2018
Last Update Posted : November 1, 2018
Sponsor:
Information provided by (Responsible Party):
Transgene

Brief 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) according to a 3+3 design 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 colon 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.


Condition or disease Intervention/treatment Phase
Colon Cancer Digestive System Neoplasm Biological: TG6002 Drug: Flucytosine (5-FC, Ancotil) Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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.
Actual Study Start Date : October 16, 2018
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Flucytosine

Arm Intervention/treatment
Experimental: TG6002 and flucytosine combination Biological: TG6002

Phase I: Dose escalation from 1 x 10E6 PFU to 3 x 10E8 PFU Phase II: Established recommended Phase II dose (RP2D)

Administration intravenously on Days 1, 8 and 15. 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.


Drug: Flucytosine (5-FC, Ancotil)

Administered orally at a dose of 200 mg/kg/day from Day 5 to 7, Day 12 to 14 and Day 19 to 28.

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.





Primary Outcome Measures :
  1. Phase I part - Dose-limiting toxicities [ Time Frame: Day 28 ]
    Dose-limiting toxicities

  2. Phase II part - Overall response rate [ Time Frame: Day 43 ]
    Overall response rate according to Recist v1.1



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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 colon 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.
  2. Male or female aged ≥18 years
  3. Patient presenting with at least one measurable lesion according to RECIST 1.1 in Phase IIa part (optional in the Phase I part)
  4. Expected survival of at least 12 weeks
  5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  6. Absolute neutrophil count (ANC) ≥1000/mm3
  7. Blood lymphocyte count ≥500/mm3
  8. Hemoglobin (Hb) level ≥10 g/dL
  9. Platelet count ≥100,000/mm3
  10. Total bilirubin ≤1.5 x Upper Limit of Normal (ULN)
  11. AST, ALT, alkaline phosphatase ≤3 x ULN
  12. Clearance for study participation and anti-hypertensive therapy suspension if any (see exclusion criterion 13) after cardiology consultation and cardiologic investigations including troponin T or I blood level, electrocardiogram (ECG) and cardiac echography (ECHO)
  13. Negative blood pregnancy test for women of childbearing potential (WOCBP)
  14. 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
  15. Signed written informed consent in accordance to ICH-GCP and national/local regulation

Exclusion Criteria:

  1. Previous irradiation of target tumor
  2. MSI-High/dMMR colon cancer patients
  3. Glomerular filtration rate <60 mL/min/1.73m2 according to the Modification of Diet in Renal Diseases (MDRD) formula
  4. 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
  5. 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
  6. Significant impairment of GI tract absorption, such as total gastrectomy, gastric mucosal atrophy, extensive intestinal resections or malabsorption disease
  7. Symptomatic bacterial intestinal overgrowth consecutive to intestinal dysmotility, surgical resections (blind loops, ileo-cecal valve), or anatomical abnormalities
  8. Inflammatory bowel disease (IBD) and bowel sub-obstruction
  9. Known deficiency in dihydropyrimidine dehydrogenase (DPD)
  10. Known hypersensitivity to 5-FC or its excipients
  11. Known hypersensitivity to eggs or gentamycin
  12. 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
  13. Inability to withdraw anti-hypertensive therapy 24 hours prior to and up to 24 hours after TG6002 treatment
  14. 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
  15. Systemic anti-cancer therapy or resection surgery within 4 weeks prior to first administration of TG6002
  16. Prior participation in another clinical study involving an IMP with last intake within 4 weeks prior to TG6002 treatment initiation
  17. 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
  18. Prior gene therapy
  19. Concurrent antiviral therapy active on vaccinia viruses (e.g. ribavirin)
  20. Nursing (e.g. lactating) females
  21. History of severe systemic reaction or side-effect after a smallpox vaccination, such as systemic vaccinia, eczema vaccinatum, encephalitis, myocarditis, pericarditis
  22. Any psychological, familiar, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
  23. Patient unable or unwilling to comply with the protocol requirements

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03724071


Contacts
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Contact: Transgene EU, Clinical Operations Department + 33 3 88 27 91 00 clinicaltrials@transgene.fr

Locations
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Belgium
Site No 0201 Recruiting
Brussels, Belgium
France
Site No 0101 Recruiting
Lyon, France
Germany
Site No 0501 Not yet recruiting
Mainz, Germany
Spain
Site No 0701 Recruiting
Madrid, Spain
Site No 0702 Recruiting
Madrid, Spain
Sponsors and Collaborators
Transgene

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Responsible Party: Transgene
ClinicalTrials.gov Identifier: NCT03724071     History of Changes
Other Study ID Numbers: TG6002.02
First Posted: October 30, 2018    Key Record Dates
Last Update Posted: November 1, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Neoplasms
Neoplasms by Site
Neoplasms
Gastrointestinal Diseases
Flucytosine
Antifungal Agents
Anti-Infective Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action