This is a neoadjuvant Phase 2a, open-label trial in patients with metastatic colorectal carcinoma who are undergoing a complete resection of the metastatic colorectal tumors in their liver.
Patients will receive either an intravenous infusion or an intratumoral injection of JX-594 (Pexa-Vec) directly into one liver lesions at Day 1. Patients will undergo a complete resection of all liver tumors at Day 15. Patients will then be monitored throughout their life for disease recurrence and/or general overall survival.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
2
intratumoral or intravenous dosage: 10e9 pfu Intravenous: administered over 60 minutes Intratumoral: direct injection into a single liver lesion
Ottawa Hospital and Research Institute (OHRI)
Ottawa, Ontario, Canada
Delivery to and replication within tumors
IT injection: replication and dissemination of JX-594 following injection of a single colorectal metastasis within the liver. A positive replication response is defined as a \> 2-fold increase in viral genome concentration in the blood(as measured in the first 12 hours following injection) within the first 14 days following treatment. Note: Viral genomes will be measured in the blood by Q-PCR at baseline, on Day 1 (15 minutes, 3 hours \& 8 hours) post-treatment and on Days 3, 5, 8, 11 and 15. IV infusion: assessment of viral gene \& protein expression in histologic samples of tumor tissue
Time frame: Day 1, 3, 5, 8, 11, and 15
JX-594 spread to, and replication within, non-injected tumors after IT JX-594 injection
JX-594 spread to, and replication within, non-injected tumors after IT JX-594 injection as measured by the presence of viral protein expression and/or LacZ expression in non-injected tumor sections from at least 1) two different non-consecutive cuts, both of which contain viable tumor tissue in at least 10 high power fields; and 2) at least 5 cells in one high power field show positive staining for viral protein and/ or LacZ expression
Time frame: Day 1
Modified Choi response assessment
Modified Choi response assessment based on DCE-MRI at baseline and between Days 8 14 (within 7 days prior to surgical resection)
Time frame: Day 8-14
Toxicity: Grade I-IV Adverse Events (according to CTCAE)
Toxicity: Grade I-IV Adverse Events (according to CTCAE); including surgical complications such as delay of surgery, prolonged hospitalization, bleeding (monitor transfusion requirements), postoperative infections, bile leak, hepatic failure sepsis and death
Time frame: Day 1- Day 43
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.