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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01394939
Recruitment Status : Completed
First Posted : July 15, 2011
Last Update Posted : January 8, 2016
Information provided by (Responsible Party):
SillaJen, Inc. ( Jennerex Biotherapeutics )

Brief Summary:
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 or disease Intervention/treatment Phase
Colorectal Carcinoma CRC Biological: JX-594 Drug: Irinotecan Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 52 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (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.
Study Start Date : January 2012
Actual Primary Completion Date : June 2015
Actual Study Completion Date : October 2015

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. 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 ]
    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.

  2. 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. ]
    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).

  3. Determine radiographic response rate of patients enrolled in the Phase 2a portion of the study [ Time Frame: Scans Every 8 weeks until Progression ]
    RECIST and Choi response criteria

Secondary Outcome Measures :
  1. Progression Free Disease [ Time Frame: CT scans every 8 weeks until Progression ]
    CT scans performed every 8 weeks until documented tumor progression.

  2. Survival [ Time Frame: Monthly until Death or Lost-to-Followup ]
    Compare overall survival time of patients treated with JX-594 alone or in combination with Irinotecan.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
  • Active cardiovascular disease, including but not limited to significant coronary artery disease (e.g., requiring angioplasty or stenting) or congestive heart failure within the preceding 12 months
  • 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
  • Inability to suspend treatment with anti-hypertensive medication for 48 hours prior to and 48 hours after all JX-594 treatments.
  • Pregnant or nursing an infant
  • Diagnosis of chronic inflammatory bowel disease and/or bowel obstruction.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01394939

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United States, Arizona
Mayo Clinic
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
Canada, Ontario
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
Hôpital Hautepierre
Strasbourg, France, 67098
Institut Claudius Regaud
Toulouse, France, 31052
Sponsors and Collaborators
Jennerex Biotherapeutics
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Study Director: James Burke, MD Jennerex Biotherapeutics
Principal Investigator: Derek Jonker, MD Ottawa Hospital and Research Institute

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Responsible Party: Jennerex Biotherapeutics Identifier: NCT01394939     History of Changes
Other Study ID Numbers: JX594-CRC019
First Posted: July 15, 2011    Key Record Dates
Last Update Posted: January 8, 2016
Last Verified: January 2016
Keywords provided by SillaJen, Inc. ( Jennerex Biotherapeutics ):
Vaccinia Virus
Colorectal Carcinoma
Colorectal cancer
Colon Cancer
Rectal Cancer
oncolytic virus
viral therapy
RAS mutant
Erbitux failure
Oxaliplatin failure
FOLFOX failure
FOLFIRI failure
Irinotecan failure
Additional relevant MeSH terms:
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Colorectal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
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
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents