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

Phase 1

Terminated

• Conditions: Colorectal Neoplasms
• Interventions: Biological: TG6002; Drug: Flucytosine (5-FC)

• Registration Number: NCT04194034
• Lead Sponsor: Transgene

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-12-08
• Study First Submitted QC: 2019-12-10
• Study First Posted: 2019-12-11
• Study Start: 2020-01-17
• Primary Completion: 2023-02-23
• Study Completion: 2023-02-23
• Status Verified: 2023-06
• Last Update Submitted: 2023-06-21
• Last Update Posted: 2023-06-23

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 15

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TG6002 and flucytosine (5-FC) combination	Flucytosine (5-FC)	-
TG6002 and flucytosine (5-FC) combination	TG6002	-

Primary Outcome Measures

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

Trial Locations

Locations (3)

Centre Léon Bérard; 🇫🇷 Lyon, France

Institut Gustave Roussy; 🇫🇷 Villejuif, France

NHS St James's University Hospital; 🇬🇧 Leeds, United Kingdom