Intra-pleural Administration of GL-ONC1, a Genetically Modified Vaccinia Virus, in Patients With Malignant Pleural Effusion: Primary, Metastases and Mesothelioma
The purpose of this study is to test the safety of the GL-ONC1 vaccinia virus at different dose levels. The investigators want to find out what effects, good and/or bad, it has on the patient and the malignant pleural effusion. A malignant pleural effusion is a build up of fluid in the chest cavity cause by the cancer.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of Intra-pleural Administration of GL-ONC1, a Genetically Modified Vaccinia Virus, in Patients With Malignant Pleural Effusion: Primary, Metastases and Mesothelioma|
- Maximum Tolerated Dose (MTD) [ Time Frame: 2 years ] [ Designated as safety issue: No ]MTD is to provide a dosing recommendation for subsequent Phase II studies. Three patients will be enrolled in each cohort at the dose levels shown in the table below in order to determine the Maximum Tolerated Dose (MTD). At the beginning of a new dose level, only one patient will be treated. The first patient in each cohort must be treated and complete 14 days of post-treatment evaluation prior to the treatment of the remaining two patients in that cohort.
- safety [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]The safety, tolerability and feasibility of GL-ONC1 will be assessed by the evaluation of the type, frequency, and severity of adverse events (AEs), changes in clinical laboratory tests (hematological and chemistry), immunogenicity and physical examination. All AEs and laboratory toxicities will be graded on the CTCAE (version 4).
- detection of virus in body fluids [ Time Frame: days 2, 3, 4, & 5. pretreatment ] [ Designated as safety issue: No ]Patients will undergo serial sampling of blood, sputum, urine samples and pleural drainage for evaluation of viral particles by VPA immediately before treatment, and on days 2, 3, 4 and 5 pretreatment.
- evaluation of viral appearance in tumor [ Time Frame: 2-9 days after intrapleural instillation of virus ] [ Designated as safety issue: No ]Unless medically contraindicated, patients will undergo Video-Assisted Thoracic Surgery (VATS) with pleural biopsies to assess for green fluorescent protein (GFP) viral expression in tumor and surrounding tissues, and if appropriate, to perform pleurodesis at 2-7 days after intrapleural instillation of virus. Random pleural biopsies and GFP-directed biopsies will be performed to allow for assessment of viral presence. Viral plaque assays (VPA) will be performed in tumor biopsies. Immunohistochemical (IHC) and beta-glucuronidase assay staining for GL-ONC1 will be performed on both GFP (-) and (+) areas at videothoracoscopy (if applicable).
- Therapeutic efficacy [ Time Frame: day 60 post treatment (+/-10 days) ] [ Designated as safety issue: No ]Therapeutic efficacy will be investigated with CT scans pretreatment and at Day 60 (+/-10) posttreatment. Response by RECIST criteria (and by modified RECIST - for mesothelioma tumors) will be summarized for each dose level using descriptive statistics.
|Study Start Date:||January 2013|
|Estimated Study Completion Date:||January 2016|
|Estimated Primary Completion Date:||January 2016 (Final data collection date for primary outcome measure)|
This is an open-label, dose-escalating, non-randomized, single-center Phase I therapeutic study of GL-ONC1 originally administered intrapleurally as a single dose and now escalating to three consecutive daily doses in patients with a diagnosis (histologically or cytologically documented) of malignant pleural effusions.
Patients will be enrolled in groups of three and individually assessed for safety and dose limiting toxicity (DLT).
Please refer to this study by its ClinicalTrials.gov identifier: NCT01766739
|Contact: Valerie Rusch, MD||212-639-5873|
|Contact: Lee Krug, MD||646-888-4201|
|United States, New York|
|Memorial Sloan Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10065|
|Contact: Valerie Rusch, MD 212-639-5873|
|Contact: Lee Krug, MD 646-888-4201|
|Principal Investigator: Valerie Rusch, MD|
|Principal Investigator:||Valerie Rusch, MD||Memorial Sloan Kettering Cancer Center|