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Study of Intrahepatic Arterial Infusion of TG6002 in Combination With 5-FC in Patients With Metastatic Colorectal Cancer

Primary Purpose

Colorectal Neoplasms

Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
TG6002
Flucytosine (5-FC)
Sponsored by
Transgene
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Neoplasms

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Unresectable metastatic CRC with at least one measurable liver metastasis
  2. At least one liver metastasis amenable to biopsy
  3. Patients previously exposed to fluoropyrimidine-based chemotherapy
  4. (Phase I) Patients having failed, are intolerant to, or unsuitable for both oxaliplatin and irinotecan-based chemotherapy, or, in the UK only, patients on or entering a period of clinical observation without treatment
  5. (Phase IIa) Patients having failed, are intolerant to, or unsuitable for both oxaliplatin and irinotecan-based chemotherapy.
  6. Aged ≥18 years
  7. Estimated life expectancy >3 months
  8. ECOG performance status ≤1

Exclusion Criteria:

  1. Predominant extrahepatic disease
  2. Symptomatic brain metastases or meningeal tumors
  3. Any contraindication to intrahepatic artery infusion procedure
  4. Received other investigational therapy or had surgery within 4 weeks of treatment initiation which would interfere with study treatment
  5. Received locoregional therapy for CRC within 4 weeks prior to treatment initiation
  6. Severe uncontrolled coagulopathy OR anticoagulant medication
  7. Antiviral therapy active on vaccinia virus, e.g., ribavirin, interferon/pegylated interferon
  8. Immunosuppression due to immunosuppressive medication including steroids equivalent to prednisolone >10mg/day taken for more than 4 weeks within 3 months prior to TG6002 treatment initiation
  9. Patients treated with 3 or more anti-hypertensive agents AND/OR patients with signs of advanced hypertensive disease, such as left ventricular hypertrophy, hypertensive encephalitis or history of hemorrhagic stroke.

Sites / Locations

  • Centre Léon Bérard
  • Institut Gustave Roussy
  • NHS St James's University Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

TG6002 and flucytosine (5-FC) combination

Arm Description

Outcomes

Primary Outcome Measures

Dose-limiting toxicities (Phase I part)
Incidence of Adverse events using CTCAE v5.0
Disease Control Rate (Phase II part)
Proportion of patients whose tumour assessment is either complete response (CR), partial response (PR), or stable disease (SD)

Secondary Outcome Measures

Full Information

First Posted
December 8, 2019
Last Updated
June 21, 2023
Sponsor
Transgene
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1. Study Identification

Unique Protocol Identification Number
NCT04194034
Brief Title
Study of Intrahepatic Arterial Infusion of TG6002 in Combination With 5-FC in Patients With Metastatic Colorectal Cancer
Official Title
A Dose-escalation and Phase IIa Study of TG6002 Plus Flucytosine in Patients With Unresectable Colorectal Cancer With Liver Metastases
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Terminated
Why Stopped
Study has been terminated after Phase I part on 23 February 2023
Study Start Date
January 17, 2020 (Actual)
Primary Completion Date
February 23, 2023 (Actual)
Study Completion Date
February 23, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Transgene

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study will include two parts: Phase I part is a dose-escalation study to assess the safety of increasing doses of TG6002 in combination with oral flucytosine (5-FC) in consecutive cohorts of 3 to 6 patients with colorectal cancer and unresectable liver metastases according to a 3+3 design Phase IIa part is an extension of the phase I part at the recommended phase II dose to evaluate the efficacy of TG6002 in combination with oral flucytosine (5-FC) in patients with colorectal cancer and unresectable liver metastases. In both parts, tumor response will be evaluated on local assessment using RECIST 1.1. All patients will be followed until disease progression, death due to any cause or the date of data cut-off, whichever occurs first.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Neoplasms

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
TG6002 and flucytosine (5-FC) combination
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
TG6002
Intervention Description
Phase I part: Dose escalation from 1 x 10E6 PFU to 1 x 10E9 PFU. Phase II part: Established recommended Phase II dose (RP2D). Intrahepatic arterial (IHA) administration on Day 1 within a 14-day cycle of TG6002/5-FC combination treatment. A second cycle of TG6002/5-FC combination starting with TG6002 (IHA) administration at the same dose on Day43 can be initiated if no progressive disease or Dose Limiting Toxicity event in between; maximum 2 cycles of TG6002/5-FC combination treatment for each patient.
Intervention Type
Drug
Intervention Name(s)
Flucytosine (5-FC)
Intervention Description
Oral administration 4 times per day at the total dose of 200 mg/kg/day for 10 consecutive days per 14-day cycle of TG6002/5-FC combination. A second cycle of TG6002/5-FC combination will be initiated if no progressive disease or Dose Limiting Toxicity event in between.
Primary Outcome Measure Information:
Title
Dose-limiting toxicities (Phase I part)
Description
Incidence of Adverse events using CTCAE v5.0
Time Frame
Day 28
Title
Disease Control Rate (Phase II part)
Description
Proportion of patients whose tumour assessment is either complete response (CR), partial response (PR), or stable disease (SD)
Time Frame
Week 10

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Unresectable metastatic CRC with at least one measurable liver metastasis At least one liver metastasis amenable to biopsy Patients previously exposed to fluoropyrimidine-based chemotherapy (Phase I) Patients having failed, are intolerant to, or unsuitable for both oxaliplatin and irinotecan-based chemotherapy, or, in the UK only, patients on or entering a period of clinical observation without treatment (Phase IIa) Patients having failed, are intolerant to, or unsuitable for both oxaliplatin and irinotecan-based chemotherapy. Aged ≥18 years Estimated life expectancy >3 months ECOG performance status ≤1 Exclusion Criteria: Predominant extrahepatic disease Symptomatic brain metastases or meningeal tumors Any contraindication to intrahepatic artery infusion procedure Received other investigational therapy or had surgery within 4 weeks of treatment initiation which would interfere with study treatment Received locoregional therapy for CRC within 4 weeks prior to treatment initiation Severe uncontrolled coagulopathy OR anticoagulant medication Antiviral therapy active on vaccinia virus, e.g., ribavirin, interferon/pegylated interferon Immunosuppression due to immunosuppressive medication including steroids equivalent to prednisolone >10mg/day taken for more than 4 weeks within 3 months prior to TG6002 treatment initiation Patients treated with 3 or more anti-hypertensive agents AND/OR patients with signs of advanced hypertensive disease, such as left ventricular hypertrophy, hypertensive encephalitis or history of hemorrhagic stroke.
Facility Information:
Facility Name
Centre Léon Bérard
City
Lyon
ZIP/Postal Code
69008
Country
France
Facility Name
Institut Gustave Roussy
City
Villejuif
ZIP/Postal Code
94800
Country
France
Facility Name
NHS St James's University Hospital
City
Leeds
ZIP/Postal Code
LS9 7TF
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Study of Intrahepatic Arterial Infusion of TG6002 in Combination With 5-FC in Patients With Metastatic Colorectal Cancer

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