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Trial record 2 of 3782 for:    colon cancer AND Intestinal Neoplasms

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

Tracking Information
First Submitted Date  ICMJE October 16, 2018
First Posted Date  ICMJE October 30, 2018
Last Update Posted Date November 1, 2018
Actual Study Start Date  ICMJE October 16, 2018
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 29, 2018)
  • Phase I part - Dose-limiting toxicities [ Time Frame: Day 28 ]
    Dose-limiting toxicities
  • Phase II part - Overall response rate [ Time Frame: Day 43 ]
    Overall response rate according to Recist v1.1
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03724071 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of TG6002 (VV TK-RR-FCU1) in Combination With 5-FC in Patients With Advanced Gastro-intestinal Tumors.
Official Title  ICMJE 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.
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Colon Cancer
  • Digestive System Neoplasm
Intervention  ICMJE
  • 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.

Study Arms  ICMJE Experimental: TG6002 and flucytosine combination
Interventions:
  • Biological: TG6002
  • Drug: Flucytosine (5-FC, Ancotil)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 29, 2018)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Transgene EU, Clinical Operations Department + 33 3 88 27 91 00 clinicaltrials@transgene.fr
Listed Location Countries  ICMJE Belgium,   France,   Germany,   Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03724071
Other Study ID Numbers  ICMJE TG6002.02
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Transgene
Study Sponsor  ICMJE Transgene
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Transgene
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP