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

• ClinicalTrials.gov Identifier: NCT04194034
• Recruitment Status: Recruiting
• First Posted: December 11, 2019
• Last Update Posted: August 25, 2021
• Sponsor: Transgene
• Information provided by (Responsible Party): Transgene

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.

Condition or disease	Intervention/treatment	Phase
Colorectal Neoplasms	Biological: TG6002; Drug: Flucytosine (5-FC)	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 75 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Dose-escalation and Phase IIa Study of TG6002 Plus Flucytosine in Patients With Unresectable Colorectal Cancer With Liver Metastases
• Actual Study Start Date: January 17, 2020
• Estimated Primary Completion Date: March 2023
• Estimated Study Completion Date: September 2023

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Transgene EU, Clinical Operations Department; +333 88 27 91 00; clinicaltrials@transgene.fr

Locations

France

Centre Léon Bérard; Recruiting

Lyon, France, 69008

Institut Gustave Roussy; Not yet recruiting

Villejuif, France, 94800

United Kingdom

NHS St James's University Hospital; Recruiting

Leeds, United Kingdom, LS9 7TF

Sponsors and Collaborators

Transgene

More Information

• Responsible Party: Transgene
• ClinicalTrials.gov Identifier: NCT04194034
• Other Study ID Numbers: TG6002.03
• First Posted: December 11, 2019
• Last Update Posted: August 25, 2021
• Last Verified: August 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Flucytosine; Antifungal Agents; Anti-Infective Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action