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

Jennerex Biotherapeutics

Status and phase: Completed; Phase 2; Phase 1

Conditions: Colorectal Carcinoma; CRC

Treatments: Drug: Irinotecan; Biological: JX-594

Study type: Interventional

Funder types: Industry

Identifiers

NCT01394939

JX594-CRC019

Details and patient eligibility

About

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.

Full description

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

Enrollment: 52 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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52 participants in 4 patient groups

Single Agent_ Cohort 1

Experimental group

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

Treatment:

Biological: JX-594

Single Agent_Cohort 2

Experimental group

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

Treatment:

Biological: JX-594

Combination_Cohort 3

Experimental group

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.

Treatment:

Biological: JX-594

Drug: Irinotecan

Combination_Cohort 4

Experimental group

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.

Treatment:

Biological: JX-594

Drug: Irinotecan