Clinical trial NCT04194034: 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
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Colorectal Neoplasms
Lead sponsor: Transgene
Sponsor class: INDUSTRY
First posted: 2019-12-11
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Dose-limiting toxicities (Phase I part)
timeFrame: Day 28
measure: Disease Control Rate (Phase II part)
timeFrame: Week 10
Secondary outcomes:
Other outcomes:
Locations:
city: Lyon
country: France
facility: Centre Léon Bérard
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Leeds
country: United Kingdom
facility: NHS St James's University Hospital
Study officials:
References: