Solid Organ Cancers
Conditions
Keywords
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
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.
Interventions
BIOLOGICALGL-ONC1
Dose and Regimen: 1. Single dose group: Cohort 1 dose is 1 × 109 pfu 2. 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.
Sponsors
Genelux Corporation
Andrew Lowy
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Level of anti-vaccinia neutralizing antibodies in serum | 2.5 years | Level of anti-vaccinia neutralizing antibodies in serum |
| 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 |
| The maximum concentration (Cmax) of GL-ONC1 in blood after administration | 2.5 years | The maximum concentration (Cmax) of GL-ONC1 in blood after administration |
| Amount of lymphocyte infiltration in pre-treatment biopsy and post-treatment resected tumor tissue | 2.5 years | Amount of lymphocyte infiltration in pre-treatment biopsy and post-treatment resected |
Countries
United States
Outcome results
None listed