Safety Study of GL-ONC1, an Oncolytic Virus, in Patients With Advanced Solid Tumors
The main purpose of this study is to determine whether, GL-ONC1, an Oncolytic Virus, can safely be administered intravenously in patients with advanced solid tumors.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of the Safety, Tolerability,and Tumor-Specific Replication of the Intravenous Administration of Green Fluorescent Protein Encoded Genetically Engineered Attenuated Vaccinia Virus, GL-ONC1, in Patients With Advanced Solid Organ Cancers.|
- Determine the safety and tolerability of GL-ONC1, administered intravenously to patients with advanced solid tumors. [ Time Frame: Every 30 minutes for 2 hours after each administration of GL-ONC1, then daily until discharge and on day 8, then weekly up to day 21, then week 12 and week 24 ] [ Designated as safety issue: Yes ]
- Detection of virus delivery to primary and/or metastatic tumors by PCR and immunohistochemistry. [ Time Frame: To be performed where tumor is deemed safely accessible for biopsy (requires patient consent). Timing of post-treatment biopsy may vary to optimise data generated, however, within two weeks of administration is considered suitable. ] [ Designated as safety issue: No ]
- Evaluation of anti-vaccinia virus immune response (antibody responses) [ Time Frame: To be done at baseline and weekly for the first 8 weeks for all cohorts. A final test will be performed on day 30 after the last virus application. ] [ Designated as safety issue: No ]
- Evaluation of viral delivery by fluorescence imaging [ Time Frame: The timing and frequency of visualization will be dependent on the acquired data but may be pursued once weekly for the length of the observation period. ] [ Designated as safety issue: No ]
- Determine recommended dose and schedule for future investigation. [ Time Frame: At the end of the study ] [ Designated as safety issue: Yes ]
- Evaluation of anti-tumor activity [ Time Frame: Week 12 and week 24 after each cycle (Cohorts 1-7). Cohort 8, 1B: 15 days (± 3 days),on D 29 (± 3 days) prior to Cycle 2 ;CT: weeks 12, 24 ] [ Designated as safety issue: No ]Generally CT scan (conventional or spiral), PET/CT, MRI or clinical examination will be used for patients in Cohorts 1-7, however tumor markers can also be used to assess response. For patients enrolled in Cohort 8 and the Phase IB expansion cohort of this trial, tumor evaluation will also be performed by DCE and DW-MRIs as well as FDG-PET-CT and CT scans. RECIST and modified CHOI criteria for response will be employed in image evaluations.
- Determine possible predictive value of Circulating Tumor Cell counts and Beta-glucuronidase levels relative to patient survival outcomes. [ Time Frame: CTC's: baseline, Cycle 1 Day 8, prior to dosing D 1 of Cycles 2, 3, 4. Beta-glucuronidase analysis: baseline , weekly first 2 cycles, monthly pre-dose for following cycles;.Final test day 30 after last treatment ] [ Designated as safety issue: No ]Circulating Tumor Cells are present in patients with advanced metastatic solid tumor cancers. Beta-glucomidase analysis will be used to determine expression of the virus encoded marker genes. CTC counts and Beta-glucomidase values together may be a prognostic indicator (measure of survival outcomes) for patients with solid tumors.
- Assess correlation of CTC number with radiological (imaging) as early pharmacodynamic and response rate indicators for GL-ONC1 treatment. [ Time Frame: CTC's: baseline, Cycle 1 Day 8, prior to dosing Day 1 of Cycles 2, 3, 4. Imaging: DCE, DW-MRIs and FDG-PET-CT at baseline, 15 days, on Day 29 prior to administration of Cycle 2; CT scans: weeks 12,24. ] [ Designated as safety issue: No ]For patients in Cohort 8 and a Phase 1B expansion study group who have high circulating blood cell counts and solid tumors that may be safely, serially biopsied, the study seeks to demonstrate the correlation of CTC number with radiological outcomes, including Dynamic Contrast Enhanced (DCE) and Diffusion Weighted (DW) magnetic resonance imaging (MRI) and fluoro-deoxy glucose (FDG)-positron emission tomography (PET)-computed tomography (CT) scan changes as early pharmacodynamic and response rate indicators in the GL-ONC1 treatment context.
|Study Start Date:||November 2008|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||November 2015 (Final data collection date for primary outcome measure)|
In preclinical studies, GL-ONC1 an oncolytic vaccinia virus, has shown the ability to preferentially locate, colonize and destroy tumor cells. This study seeks to evaluate the safety profile of an attenuated vaccinia virus when administered intravenously to patients with advanced solid tumors. The study also seeks to detect virus delivery to primary and/or metastatic tumors, including evaluation of viral delivery by fluorescence imaging (GFP expression); whether anti-vaccinia virus immune response occurs; and will record evidence of any anti-tumor activity. For Cohorts 8 and Expansion Cohort 1B, CTC counts, virus-encoded marker gene analysis and Dynamic Contrast (DCE-MRI) MRI imaging will be used to evaluate tumor micro-circulation in vivo. These measures will be evaluated for their potential predictive value of survival outcomes, and to evaluate any correlation of such pharmacodynamic and response rate indicators in the GL-ONC1 treatment context.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00794131
|Contact: Johann de Bono, MD FRCP PhDfirstname.lastname@example.org|
|Royal Marsden Hospital||Recruiting|
|Surrey, United Kingdom|
|Principal Investigator:||Johann de Bono, MD FRCP MSc PhD||Royal Marsdon Hospital/Institute for Cancer Research|
|Principal Investigator:||Kevin Harrington, MBBS MRCP FRCR||Royal Marsden Hospital/Institute of Cancer Research|
|Principal Investigator:||Hardev Pandha, MD,FRCP,FRACP,PhD||Surrey Clinical Research Centre|