Safety and Effect of GL-ONC1 Administered IV Prior to Surgery to Patients With Solid Organ Cancers Undergoing Surgery

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety of the investigational product GL-ONC1. GL-ONC1, a vaccinia virus, has been genetically modified for use as a potential anti-cancer drug to destroy cancer cells. Vaccinia virus has been used successfully in the past as smallpox vaccine in millions of people worldwide.

Detailed Description
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This is an open-label, non-randomized Phase 1b dose escalation study evaluating the safety and effect of the oncolytic virus GL-ONC1 administered intravenously, with or without eculizumab, prior to surgery in patients with advanced solid organ tumors. GL-ONC1 is a genetically engineered oncolytic vaccinia virus, which disrupts nonessential genes and expression of the foreign gene expression. Evidence suggest that GL-ONC1 is able to infect tumor tissue and kill tumor cells. The goals of this study are to evaluate the safety of GL-ONC1 and to assess the pharmacokinetics and pharmacodynamics profile of GL-ONC1 in vivo.

Official Title
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An Open Label, Non-randomized Phase 1b Study to Investigate the Safety and Effect of the Oncolytic Virus GL-ONC1 Administered Intravenously Prior to Surgery to Patients With Solid Organ Cancers Undergoing Surgery for Curative-Intent or Palliative Resection

Conditions
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Solid Organ Cancers

Intervention / Treatment
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* Biological: GL-ONC1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically-proven diagnosis of advanced (AJCC, 7th Edition: stage III or IV) or aggressive solid organ cancer. Patients must provide written consent for a core needle biopsy sample of tumor tissue (primary or metastatic). Have evidence of measurable disease (according to RECIST Version 1.1: http:// www.recist.com). Have an ECOG Performance Score of 0 to 2. Have a life expectancy of at least 3 months. Have adequate organ and marrow function Negative serum pregnancy test for females of childbearing potential. Have negative test result for HIV and Hepatitis B or C testing. Have baseline anti-vaccinia antibody titer < 10. Exclusion Criteria: Current or anticipated use of other investigational agents or marketed anticancer agent while on study (from the time of enrollment through the time of surgery). Patients who have received chemotherapy or radiotherapy within 4 weeks prior to entering the study. Small pox vaccination for 4 weeks before study therapy and during study treatment. Have received prior gene therapy or therapy with cytolytic virus of any type. Have clinically significant cardiac disease Oxygen saturation <90% measured by pulse oximetry at rest. Receiving concurrent antiviral agent active against vaccinia virus (e.g., cidofovir, vaccinia immunoglobulin, imatinib, ST-246) during the course of study. Have known allergy to ovalbumin or other egg products. Have clinically significant dermatological disorders (e.g., eczema, psoriasis, or any unhealed skin wounds or ulcers) Have a history of allergy to iodinated contrast media. Patients with known brain metastases Pregnant or nursing

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GL-ONC1<br>Cohort 3, 5, 7, 8, 9 | Biological: GL-ONC1<br>* Dose and Regimen: Single dose group: Cohort 1 dose is 1 × 109 pfu Multiple dose groups: Cohort 2 dose is 1 × 109 pfu × 5 consecutive days Cohorts 3 and 4 dose is 2 × 109 pfu × 5 consecutive days Cohorts 5 and 6 dose escalates at 2,3,5,5,5 × 109 pfu. Route: GL-ONC1 is delivered as a bolus IV injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as defined by CTCAE v4.03. |  | 2.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The presence of GL-ONC1 within malignant tumors by examination of the resected surgical specimen. |  | 2.5 years | 
| The maximum concentration (Cmax) of GL-ONC1 in blood after administration |  | 2.5 years | 
| Level of anti-vaccinia neutralizing antibodies in serum |  | 2.5 years | 
| Amount of lymphocyte infiltration in pre-treatment biopsy and post-treatment resected tumor tissue |  | 2.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GL-ONC1, Solid Organ Cancer, Cancer, Surgery, Oncolytic Virus, Soliris, Metastatic melanoma, Esophageal and gastric adenocarcinoma (Stage III/IV), Cholangiocarcinoma, Pancreatic adenocarcinoma, Gallbladder cancer, Colorectal cancer (Stage IV), High-grade mucinous appendix cancer, High-grade gastrointestinal neuroendocrine cancer, Mesothelioma, High-grade soft tissue sarcoma, Stage III or IV