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

A Dose-escalation and Phase IIa Study of TG6002 Plus Flucytosine in Patients With Unresectable Colorectal Cancer With Liver Metastases

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.

Study Overview

• Status: Terminated
• Conditions: Colorectal Neoplasms
• Intervention / Treatment: Biological: TG6002; Drug: Flucytosine (5-FC)

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Transgene EU, Clinical Operations Department; Phone Number: +333 88 27 91 00; Email: clinicaltrials@transgene.fr

Study Locations

• France
  • Lyon, France, 69008
    • Centre Léon Bérard
  • Villejuif, France, 94800
    • Institut Gustave Roussy
• United Kingdom
  • Leeds, United Kingdom, LS9 7TF
    • NHS St James's University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: TG6002 and flucytosine (5-FC) combination

Biological: TG6002; 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.; Drug: Flucytosine (5-FC); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicities (Phase I part)	Incidence of Adverse events using CTCAE v5.0	Day 28
Disease Control Rate (Phase II part)	Proportion of patients whose tumour assessment is either complete response (CR), partial response (PR), or stable disease (SD)	Week 10

Collaborators and Investigators

• Sponsor: Transgene

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2020
• Primary Completion (Actual): February 23, 2023
• Study Completion (Actual): February 23, 2023

Study Registration Dates

• First Submitted: December 8, 2019
• First Submitted That Met QC Criteria: December 10, 2019
• First Posted (Actual): December 11, 2019

Study Record Updates

• Last Update Posted (Actual): June 23, 2023
• Last Update Submitted That Met QC Criteria: June 21, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antimetabolites; Antifungal Agents; Flucytosine
• Other Study ID Numbers: TG6002.03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No