Recombinant Vaccinia Virus Administered Intravenously in Patients With Metastatic, Refractory Colorectal Carcinoma
The purpose of this study is to evaluate the safety, tolerability, and efficacy of JX-594 (Pexa-Vec) administered intravenously either alone or in combination with Irinotecan in colorectal carcinoma patients who are refractory to or intolerant to standard therapy.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1/2a Dose-escalation Study of JX 594 (Thymidine Kinase-Deactivated Vaccinia Virus Plus GM-CSF) Administered by Multiple Intravenous (IV) Infusions Alone and in Combination With Irinotecan in Patients With Metastatic, Refractory Colorectal Carcinoma.|
- Determine the maximally-tolerated dose (MTD) or maximum feasible dose (MFD) of JX-594 administered by 5 IV infusions alone and in combination with irinotecan [ Time Frame: DLTs evaluated until Week 5/Day36 ] [ Designated as safety issue: Yes ]Any of the following treatment related adverse events: Grade 4 toxicity (except isolated G4 lymphopenia lasting ≤ 7 days), Grade 3 or 4 hypotension, disseminated intravascular coagulation (DIC) or allergic reaction/hypersensitivity, Grade 3 non-hematologic toxicity persisting for > 7 days (except for transaminitis (increase in AST and/or ALT), which may last > 7 days if total bilirubin is normal or Grade 1 or flu-like symptoms that respond to standard treatments), or Grade 3 hematologic toxicity persisting for > 7 days.
- Determine the safety of JX-594 administered by 5 IV infusions followed by up to 3 IV JX-594 boosts alone and in combination with irinotecan [ Time Frame: 28 days after last dose of JX-594 IV. ] [ Designated as safety issue: Yes ]Adverse events will be collected and assessed to assess safety and tolerability through 28 days after last dose of JX-594 (or until all events considered probably or possibly related to JX-594 have resolved, stabilized, or returned to baseline status).
- Determine radiographic response rate of patients enrolled in the Phase 2a portion of the study [ Time Frame: Scans Every 8 weeks until Progression ] [ Designated as safety issue: No ]RECIST and Choi response criteria
- Progression Free Disease [ Time Frame: CT scans every 8 weeks until Progression ] [ Designated as safety issue: No ]CT scans performed every 8 weeks until documented tumor progression.
- Survival [ Time Frame: Monthly until Death or Lost-to-Followup ] [ Designated as safety issue: No ]Compare overall survival time of patients treated with JX-594 alone or in combination with Irinotecan.
|Study Start Date:||January 2012|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||June 2014 (Final data collection date for primary outcome measure)|
Experimental: Single Agent
JX-594 administered intravenously weekly for 5 weeks followed by up to 3 additional intravenous infusion boosts.
Recombinant Vaccinia GM-CSF; RAC VAC GM-CSF (JX-594)
JX-594 administered intravenously weekly for 5 weeks followed by up to three additional intravenous infusion boosts in combination with Irinotecan administered every 14 days beginning at Day 9.
Recombinant Vaccinia GM-CSF; RAC VAC GM-CSF (JX-594)Drug: Irinotecan
180 mg/m2 IV every 2 weeks.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01394939
|United States, Arizona|
|Scottsdale, Arizona, United States, 85259-5499|
|United States, California|
|UCSD Moores Cancer Center|
|La Jolla, California, United States, 92093|
|United States, Montana|
|Billings Clinic Cancer Center|
|Billings, Montana, United States, 59101|
|United States, North Carolina|
|University of North Carolina|
|Chapel Hill, North Carolina, United States, 27599-1651|
|United States, Ohio|
|Gabrail Cancer Center|
|Canton, Ohio, United States|
|The Ohio State University|
|Columbus, Ohio, United States, 43210|
|Juravinski Cancer Centre|
|Hamilton, Ontario, Canada, L8V 5C2|
|Ottawa Hospital and Research Institute (OHRI)|
|Ottawa, Ontario, Canada, K1H 8L6|
|Hôpital Saint Antoine|
|Paris, France, 75012|
|Strasbourg, France, 67098|
|Institut Claudius Regaud|
|Toulouse, France, 31052|
|Study Director:||James Burke, MD||Jennerex Biotherapeutics|
|Principal Investigator:||Derek Jonker, MD||Ottawa Hospital and Research Institute|