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
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- Enrollment
- 5
- Locations
- 2
- Primary Endpoint
- Number of participants with treatment-related adverse events as defined by CTCAE v4.03.
Study Overview
Brief Summary
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
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
- •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
Outcomes
Primary Outcomes
Number of participants with treatment-related adverse events as defined by CTCAE v4.03.
Time Frame: 2.5 years
Number of participants with treatment-related adverse events as defined by CTCAE v4.03.
Secondary Outcomes
- The presence of GL-ONC1 within malignant tumors by examination of the resected surgical specimen.(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)
- The maximum concentration (Cmax) of GL-ONC1 in blood after administration(2.5 years)
Investigators
Andrew Lowy
Chief, Division of Surgical Oncology
University of California, San Diego