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

Phase 1

Completed

• Conditions: Colorectal Carcinoma; CRC
• Interventions: Biological: JX-594; Drug: Irinotecan

• Registration Number: NCT01394939
• Lead Sponsor: 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.

Detailed Description

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

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2011-07-13
• Study First Submitted QC: 2011-07-14
• Study First Posted: 2011-07-15
• Study Start: 2012-01
• Primary Completion: 2015-06
• Study Completion: 2015-10
• Results First Submitted: 2020-09-14
• Status Verified: 2020-12
• Results First Submitted QC: 2020-12-11
• Last Update Submitted: 2020-12-11
• Results First Posted: 2021-01-08
• Last Update Posted: 2021-01-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 52

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)

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Single Agent_ Cohort 1	JX-594	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
Single Agent_Cohort 2	JX-594	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
Combination_Cohort 3	JX-594	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.
Combination_Cohort 4	JX-594	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.
Combination_Cohort 3	Irinotecan	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.
Combination_Cohort 4	Irinotecan	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.

Primary Outcome Measures

Name	Time	Method
Determine Radiographic Response Rate of Patients Enrolled in the Phase 2a Portion of the Study	Scans Every 8 weeks until radiographic progression was confirmed by the site.	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.

Trial Locations

Locations (11)

Mayo Clinic; 🇺🇸 Scottsdale, Arizona, United States

University of North Carolina; 🇺🇸 Chapel Hill, North Carolina, United States

Hôpital Saint Antoine; 🇫🇷 Paris, France

UCSD Moores Cancer Center; 🇺🇸 La Jolla, California, United States

Billings Clinic Cancer Center; 🇺🇸 Billings, Montana, United States

Gabrail Cancer Center; 🇺🇸 Canton, Ohio, United States

Juravinski Cancer Centre; 🇨🇦 Hamilton, Ontario, Canada

The Ohio State University; 🇺🇸 Columbus, Ohio, United States

Ottawa Hospital and Research Institute (OHRI); 🇨🇦 Ottawa, Ontario, Canada

Institut Claudius Regaud; 🇫🇷 Toulouse, France

Hôpital Hautepierre; 🇫🇷 Strasbourg, France