Clinical trial NCT01394939: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: 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
Lead sponsor: SillaJen, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Transgene
First posted: 2011-07-15
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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)

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.

Primary outcomes:
measure: Determine Radiographic Response Rate of Patients Enrolled in the Phase 2a Portion of the Study
timeFrame: Scans Every 8 weeks until radiographic progression was confirmed by the site.
Secondary outcomes:
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: La Jolla
country: United States
facility: UCSD Moores Cancer Center
state: California
city: Billings
country: United States
facility: Billings Clinic Cancer Center
state: Montana
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital and Research Institute (OHRI)
state: Ontario
city: Paris
country: France
facility: Hôpital Saint Antoine
city: Strasbourg
country: France
facility: Hôpital Hautepierre
city: Toulouse
country: France
facility: Institut Claudius Regaud
Study officials:
affiliation: Jennerex Biotherapeutics
name: James Burke, MD
role: STUDY_DIRECTOR
affiliation: Ottawa Hospital and Research Institute
name: Derek Jonker, MD
role: PRINCIPAL_INVESTIGATOR
References: