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GL-ONC1 Administered Intravenously Prior to Surgery to Patients With Solid Organ Cancers

Phase 1
Terminated
Conditions
Solid Organ Cancers
Interventions
Biological: GL-ONC1
Registration Number
NCT02714374
Lead Sponsor
Andrew Lowy
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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
5
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
GL-ONC1GL-ONC1Cohort 3, 5, 7, 8, 9
Primary Outcome Measures
NameTimeMethod
Number of participants with treatment-related adverse events as defined by CTCAE v4.03.2.5 years

Number of participants with treatment-related adverse events as defined by CTCAE v4.03.

Secondary Outcome Measures
NameTimeMethod
The presence of GL-ONC1 within malignant tumors by examination of the resected surgical specimen.2.5 years

The presence of GL-ONC1 within malignant tumors by examination of the resected

Level of anti-vaccinia neutralizing antibodies in serum2.5 years

Level of anti-vaccinia neutralizing antibodies in serum

Amount of lymphocyte infiltration in pre-treatment biopsy and post-treatment resected tumor tissue2.5 years

Amount of lymphocyte infiltration in pre-treatment biopsy and post-treatment resected

The maximum concentration (Cmax) of GL-ONC1 in blood after administration2.5 years

The maximum concentration (Cmax) of GL-ONC1 in blood after administration

Trial Locations

Locations (1)

UC San Diego Moores Cancer Center

🇺🇸

La Jolla, California, United States

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