Clinical Trials /

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

NCT03724071

Description:

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.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Ampulla of Vater Carcinoma
  • Colon Carcinoma
  • Esophageal Carcinoma
  • Gastrointestinal Stromal Tumor
  • Malignant Esophagogastric Neoplasm
  • Malignant Gastric Neoplasm
  • Malignant Intestinal Neoplasm
  • Malignant Small Intestinal Neoplasm
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: TG6002.02
  • NCT ID: NCT03724071

Conditions

  • Colon Cancer
  • Digestive System Neoplasm

Interventions

DrugSynonymsArms
TG6002TG6002 and flucytosine combination
Flucytosine (5-FC, Ancotil)TG6002 and flucytosine combination

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
TG6002 and flucytosine combinationExperimental
  • TG6002
  • Flucytosine (5-FC, Ancotil)

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase I part - Dose-limiting toxicities
Time Frame:Day 28
Safety Issue:
Description:Dose-limiting toxicities

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Transgene

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