Recombinant Vaccinia Virus Administered Intravenously in Patients With Metastatic, Refractory Colorectal Carcinoma

This study is currently recruiting participants.
Verified January 2012 by Jennerex Biotherapeutics
Sponsor:
Collaborator:
Transgene
Information provided by (Responsible Party):
Jennerex Biotherapeutics
ClinicalTrials.gov Identifier:
NCT01394939
First received: July 13, 2011
Last updated: June 11, 2013
Last verified: January 2012
  Purpose

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.


Condition Intervention Phase
Colorectal Carcinoma
CRC
Biological: JX-594
Drug: Irinotecan
Phase 1
Phase 2

Study Type: Interventional
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.

Resource links provided by NLM:


Further study details as provided by Jennerex Biotherapeutics:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 42
Study Start Date: January 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single Agent
JX-594 administered intravenously weekly for 5 weeks followed by up to 3 additional intravenous infusion boosts.
Biological: JX-594
Recombinant Vaccinia GM-CSF; RAC VAC GM-CSF (JX-594)
Experimental: Combination
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.
Biological: JX-594
Recombinant Vaccinia GM-CSF; RAC VAC GM-CSF (JX-594)
Drug: Irinotecan
180 mg/m2 IV every 2 weeks.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically-confirmed, advanced metastatic colorectal cancer failed treatment with fluoropyrimidine (fluoruracil or capecitabine) and oxaliplatin based therapies or had contradictions to treatment with these drugs as determined by the investigator
  • Failed treatment with irinotecan
  • Kras mutant tumor or Kras wild-type having failed cetuximab (Erbitux) or panitumumab (Vectibix) or had contradictions to treatment
  • Regorafenib-naïve (have not received regorafenib)
  • ECOG 0, 1 or 2
  • Measurable tumor (≥1 cm longest diameter)
  • Acceptable health status as determined by the investigator and blood work (Chemistry, Complete Blood Count, Coagulation)

Exclusion Criteria:

  • Intolerant to Irinotecan (if assigned to the combination arm: Cohort 3, Cohort 4 or Combination Expansion Arm)
  • Treatment with ketoconazole, enzyme-inducing anticonvulsants and St. John's Wort (if assigned to combination arm)
  • Significant immunodeficiency due to underlying illness and/or medication
  • History of severe exfoliative skin condition requiring systemic therapy within the past 2 years
  • Clinically significant and/or rapidly accumulating ascites, pericardial and/or pleural effusions
  • Severe or unstable cardiac disease
  • Viable CNS malignancy associated with clinical symptoms
  • Received anti-cancer therapy within 4 weeks prior to first treatment (6 weeks for mitomycin c or nitrosoureas)
  • Prior participation in any other research protocol involving an investigational medicinal product within 4 weeks prior to first treatment
  • Use of prohibited anti-viral medication, interferon/pegylated interferon (PEG-IFN) or ribavirin that cannot be discontinued within 14 days prior to any JX 594 dose
  • Pregnant or nursing an infant
  • Diagnosis of chronic inflammatory bowel disease and/or bowel obstruction.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01394939

Contacts
Contact: Patient Inquiry patient_inquiry@jennerex.com

Locations
United States, Arizona
Mayo Clinic Recruiting
Scottsdale, Arizona, United States, 85259-5499
Contact: Clinical Trials Office     507-538-7623        
Principal Investigator: Thorvardur Halfdanarson, MD            
United States, California
UCSD Moores Cancer Center Recruiting
La Jolla, California, United States, 92093
Contact: Bethany Parker     858-822-5369     bparker@ucsd.edu    
Contact: Clinical Trials Office     858-822-5354     CancerCTO@ucsd.edu    
Principal Investigator: Tony Reid, MD, PhD            
United States, Montana
Billings Clinic Cancer Center Recruiting
Billings, Montana, United States, 59101
Contact: Tricia Montgomery, RN, BSN, OCN     406-435-7483     TMontgomery@billingsclinic.org    
Contact: Jorge Nieva, M.D.            
Principal Investigator: Jorge Nieva, M.D.            
United States, North Carolina
University of North Carolina Active, not recruiting
Chapel Hill, North Carolina, United States, 27599-1651
United States, Ohio
Gabrail Cancer Center Recruiting
Canton, Ohio, United States
Contact     330-492-3345     research@gabrailcancercenter.com    
Principal Investigator: Nashat Gabrail, MD            
The Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: Mark Bloomston, MD     614-293-4583     Mark.Bloomston@osumc.edu    
Contact: Sanaa Tahiri, MD, CCRC         Sanaa.Tahiri@osumc.edu    
Principal Investigator: P. Mark Bloomston, MD            
Canada, Ontario
Juravinski Cancer Centre Active, not recruiting
Hamilton, Ontario, Canada, L8V 5C2
Ottawa Hospital and Research Institute (OHRI) Recruiting
Ottawa, Ontario, Canada, K1H 8L6
Contact: Julie Wells     (613) 737-7700 ext 70211     jwells@toh.on.ca    
Contact: Catherine Fortin     (613) 737-7700 ext 72368     cfortin@toh.on.ca    
Principal Investigator: Derek Jonker, MD            
France
Hôpital Saint Antoine Recruiting
Paris, France, 75012
Contact: Sarah Dumont, MD         sarah.dumont@sat.aphp.fr    
Principal Investigator: Aimery de Gramont, MD            
Hôpital Hautepierre Not yet recruiting
Strasbourg, France, 67098
Contact: Jean-Emmanuel Kurtz, MD         j-emmanuel.kurtz@chru-strasbourg.fr    
Principal Investigator: Jean-Emmanuel Kurtz, MD            
Institut Claudius Regaud Not yet recruiting
Toulouse, France, 31052
Contact: Jean-Pierre Delord, MD         delord.jean-pierre@claudiusregaud.fr    
Principal Investigator: Jean-Pierre Delord, MD            
Sponsors and Collaborators
Jennerex Biotherapeutics
Transgene
Investigators
Study Director: James Burke, MD Jennerex Biotherapeutics
Principal Investigator: Derek Jonker, MD Ottawa Hospital and Research Institute
  More Information

No publications provided

Responsible Party: Jennerex Biotherapeutics
ClinicalTrials.gov Identifier: NCT01394939     History of Changes
Other Study ID Numbers: JX594-CRC019
Study First Received: July 13, 2011
Last Updated: June 11, 2013
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Jennerex Biotherapeutics:
Vaccinia
Vaccinia Virus
JX-594
Jennerex
Colorectal Carcinoma
Colorectal cancer
Colon Cancer
Rectal Cancer
oncolytic virus
viral therapy
RAS mutant
Erbitux failure
Oxaliplatin failure
FOLFOX failure
FOLFIRI failure
Irinotecan failure
Pexa-Vec

Additional relevant MeSH terms:
Carcinoma
Colorectal Neoplasms
Vaccinia
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Poxviridae Infections
DNA Virus Infections
Virus Diseases
Irinotecan
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on June 13, 2013