Safety Study of GL-ONC1, an Oncolytic Virus, in Patients With Advanced Solid Tumors
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|ClinicalTrials.gov Identifier: NCT00794131|
Recruitment Status : Completed
First Posted : November 19, 2008
Last Update Posted : December 14, 2015
|Condition or disease||Intervention/treatment||Phase|
|Advanced Cancers (Solid Tumors)||Biological: GL-ONC1||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||43 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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.|
|Study Start Date :||November 2008|
|Actual Primary Completion Date :||November 2015|
|Actual Study Completion Date :||November 2015|
- Biological: GL-ONC1
a genetically-engineered vaccinia virus (encoding Renilla luciferase-Aequorea green fluorescent protein fusion, β-galactosidase, and β-glucuronidase )
- 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 ]
- 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. ]
- 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. ]
- 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. ]
- Determine recommended dose and schedule for future investigation. [ Time Frame: At the end of the study ]
- 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 ]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 ]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. ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00794131
|Royal Marsden Hospital|
|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|