Recombinant Vaccinia Virus Administered Intravenously in Patients With Metastatic, Refractory Colorectal Carcinoma
Colorectal Carcinoma, CRC
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
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
Experimental
Experimental
Experimental
Experimental
Single Agent_ Cohort 1
Single Agent_Cohort 2
Combination_Cohort 3
Combination_Cohort 4
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.