A Phase 1b Dose Escalation Study of JX-594 (Thymidine Kinase-Inactivated Vaccinia Virus Plus GM-CSF) Administered by Biweekly (Every Two Weeks) Intravenous Infusion in Patients With Metastatic, Refractory Colorectal Carcinoma
This is a Phase 1b, open-label, dose-escalation trial in patients with advanced colorectal
carcinoma (CRC) that have failed both oxaliplatin based and irinotecan based prior
chemotherapy regimens for metastatic disease. Patients will receive treatment at one of
three dose levels in a sequential dose-escalating design.
Three patients will be treated at each dose level unless a dose-limiting toxicity (DLT) is
observed. Enrollment will proceed to the next dose level if 0 of 3 patients experiences a
DLT; if one of the first 3 patients experiences a DLT, additional patients will be enrolled
until a second patient experiences a DLT (which defines the toxic dose) or until six total
patients have been treated at that dose level, whichever comes first. If a second DLT is
not experienced within that cohort, dose escalation may continue.
Patients will be enrolled a minimum of 14 days after the first treatment of the immediately
preceding patient for the first patient in any cohort or all remaining patients in a cohort
If 2 DLTs are observed within a cohort, enrollment into the cohort will cease and the dose
level immediately preceding that dose will be determined to be the MTD. Regulatory
Authorities and the IRB will be notified as required if any patient dies within 28 days of
product administration due to a serious and unexpected ADR that is determined by the
Investigator to be possibly or probably related to JX-594.
Once the MTD and/or MFD is defined, an additional 3-6 patients may be enrolled at that dose
level. Note: once the MTD and/or MFD is defined, treatment of additional patients at this
dose level will no longer require inter-patient delays of 14 days.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Determine the maximally-tolerated dose
Young suk park, MD
Samsung Medical Center
Korea: Food and Drug Administration
SMC IRB 2009-06-055