search
Back to results

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

Primary Purpose

Colorectal Carcinoma, CRC

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
JX-594
Irinotecan
Sponsored by
Jennerex Biotherapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Carcinoma focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 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 Centrual Nervous System (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.

Sites / Locations

  • Mayo Clinic
  • UCSD Moores Cancer Center
  • Billings Clinic Cancer Center
  • University of North Carolina
  • Gabrail Cancer Center
  • The Ohio State University
  • Juravinski Cancer Centre
  • Ottawa Hospital and Research Institute (OHRI)
  • Hôpital Saint Antoine
  • Hôpital Hautepierre
  • Institut Claudius Regaud

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Single Agent_ Cohort 1

Single Agent_Cohort 2

Combination_Cohort 3

Combination_Cohort 4

Arm Description

JX-594 administered intravenously weekly for 5 weeks followed by up to 3 additional intravenous infusion boosts. JX-594: Recombinant Vaccinia Granulocyte-Macrophage Colony-Stimulating Factor (RAC VAC GM-CSF) Cohort 1: JX-594 3 x 10^8 plaque forming unit (pfu), Days 1, 8,15, 22, and 29

JX-594 administered intravenously weekly for 5 weeks followed by up to 3 additional intravenous infusion boosts. JX-594: RAC VAC GM-CSF Cohort 2: JX-594 1 x 10^9 pfu, Days 1, 8,15, 22, and 29

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. JX-594: RAC VAC GM-CSF Irinotecan: 180 mg/m2 IV every 2 weeks. JX-594 3 x 10^8 pfu Day 1,8, 15, 22, 29 + irinotecan 180 mg/m2 biweekly starts on Day 9.

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. JX-594: RAC VAC GM-CSF JX-594 1 x 10^9 pfu Day1, 8, 15, 22, 29 + irinotecan 180 mg/m2 biweekly starts on Day 9.

Outcomes

Primary Outcome Measures

Determine Radiographic Response Rate of Patients Enrolled in the Phase 2a Portion of the Study
Percentage of participants who showed overall response during their participation in the study. Per Modified Response Evaluation Criteria In Solid Tumors Criteria (mRECIST) and assessed by tri-phasic contrast enhanced CT: Complete Response (CR), Disappearance of intratumoral enhancing area; Partial Response (PR), >=30% decrease in the sum of the diameters of enhancing area; Overall Response (OR) = CR + PR.

Secondary Outcome Measures

Full Information

First Posted
July 13, 2011
Last Updated
December 11, 2020
Sponsor
Jennerex Biotherapeutics
Collaborators
Transgene
search

1. Study Identification

Unique Protocol Identification Number
NCT01394939
Brief Title
Recombinant Vaccinia Virus Administered Intravenously in Patients With Metastatic, Refractory Colorectal Carcinoma
Official Title
A Phase 1/2a Dose-escalation Study of JX 594 Administered by Multiple Intravenous (IV) Infusions Alone and in Combination With Irinotecan in Patients With Metastatic, Refractory Colorectal Carcinoma.
Study Type
Interventional

2. Study Status

Record Verification Date
December 2020
Overall Recruitment Status
Completed
Study Start Date
January 2012 (undefined)
Primary Completion Date
June 2015 (Actual)
Study Completion Date
October 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jennerex Biotherapeutics
Collaborators
Transgene

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
This was a Phase 1/2a, open-label, dose-escalation study in patients with advanced colorectal cancer (CRC)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Carcinoma, CRC
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
52 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Single Agent_ Cohort 1
Arm Type
Experimental
Arm Description
JX-594 administered intravenously weekly for 5 weeks followed by up to 3 additional intravenous infusion boosts. JX-594: Recombinant Vaccinia Granulocyte-Macrophage Colony-Stimulating Factor (RAC VAC GM-CSF) Cohort 1: JX-594 3 x 10^8 plaque forming unit (pfu), Days 1, 8,15, 22, and 29
Arm Title
Single Agent_Cohort 2
Arm Type
Experimental
Arm Description
JX-594 administered intravenously weekly for 5 weeks followed by up to 3 additional intravenous infusion boosts. JX-594: RAC VAC GM-CSF Cohort 2: JX-594 1 x 10^9 pfu, Days 1, 8,15, 22, and 29
Arm Title
Combination_Cohort 3
Arm Type
Experimental
Arm Description
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. JX-594: RAC VAC GM-CSF Irinotecan: 180 mg/m2 IV every 2 weeks. JX-594 3 x 10^8 pfu Day 1,8, 15, 22, 29 + irinotecan 180 mg/m2 biweekly starts on Day 9.
Arm Title
Combination_Cohort 4
Arm Type
Experimental
Arm Description
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. JX-594: RAC VAC GM-CSF JX-594 1 x 10^9 pfu Day1, 8, 15, 22, 29 + irinotecan 180 mg/m2 biweekly starts on Day 9.
Intervention Type
Biological
Intervention Name(s)
JX-594
Intervention Description
Recombinant Vaccinia GM-CSF; RAC VAC GM-CSF (JX-594)
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Intervention Description
180 mg/m2 IV every 2 weeks.
Primary Outcome Measure Information:
Title
Determine Radiographic Response Rate of Patients Enrolled in the Phase 2a Portion of the Study
Description
Percentage of participants who showed overall response during their participation in the study. Per Modified Response Evaluation Criteria In Solid Tumors Criteria (mRECIST) and assessed by tri-phasic contrast enhanced CT: Complete Response (CR), Disappearance of intratumoral enhancing area; Partial Response (PR), >=30% decrease in the sum of the diameters of enhancing area; Overall Response (OR) = CR + PR.
Time Frame
Scans Every 8 weeks until radiographic progression was confirmed by the site.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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) Eastern Cooperative Oncology Group (ECOG) Performance Status 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 Centrual Nervous System (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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James Burke, MD
Organizational Affiliation
Jennerex Biotherapeutics
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Derek Jonker, MD
Organizational Affiliation
Ottawa Hospital and Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259-5499
Country
United States
Facility Name
UCSD Moores Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
Billings Clinic Cancer Center
City
Billings
State/Province
Montana
ZIP/Postal Code
59101
Country
United States
Facility Name
University of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599-1651
Country
United States
Facility Name
Gabrail Cancer Center
City
Canton
State/Province
Ohio
ZIP/Postal Code
44718
Country
United States
Facility Name
The Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Juravinski Cancer Centre
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V 5C2
Country
Canada
Facility Name
Ottawa Hospital and Research Institute (OHRI)
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
Hôpital Saint Antoine
City
Paris
ZIP/Postal Code
75012
Country
France
Facility Name
Hôpital Hautepierre
City
Strasbourg
ZIP/Postal Code
67200
Country
France
Facility Name
Institut Claudius Regaud
City
Toulouse
ZIP/Postal Code
31052
Country
France

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs