Safety Study of Replication-competent Adenovirus (Delta-24-rgd) in Patients With Recurrent Glioblastoma
In the Netherlands a 2 center investigator-driven phase I/II clinical trial is initiated in June 2010 testing the oncolytic adenovirus Delta24-RGD to treat glioblastoma patients. The virus is administrated using convection-enhanced delivery by 4 catheters as delivery technique, targeting solid tumor as well as infiltrated tumor cells within the peri-tumoral brain. Patients will be enrolled in cohorts of 3 per dose-level. The dose levels to be explored are: 10^7, 10^8, 10^9, 10^10, 3*10^10 and 10^11 viral particles (vp). Once the MTD has been determined, or the study has reached the highest dose cohort, a further 6 or 9 patients will be enrolled at the MTD and evaluated for safety and preliminary signs of efficacy, such that in total at least 12 patients have received the MTD.
The primary objective is to determine the safety and tolerability of Delta-24-RGD administered by CED to the tumor and the surrounding infiltrated brain in patients with recurrent GBM. Secondary objectives are to determine the Progression Free Survival (PFS), Overall Survival (OS), and tumor response rate in patients with recurring tumors amenable for surgical resection and treated at the MTD.
Cerebrospinal fluid as well as brain interstitial fluid by microdialysis next to the routinely collected samples of blood at various timepoints before, during and after virus infusion. Various neurodegenerative biomarkers as well as markers of immune response will be assessed in these samples.
Furthermore extensive sampling and PCR analyses will be performed to evaluate distribution and shedding of the virus.
|Brain Tumor Recurring Glioblastoma||Biological: delta-24-RGD adenovirus||Phase 1 Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase I/II Trial of a Conditionally Replication-competent Adenovirus (Delta-24-rgd) Administered by Convection Enhanced Delivery in Patients With Recurrent Glioblastoma|
- treatment related serious adverse events [ Time Frame: untill 3 months after treatment ]
- The number of participants alive after 6 months and after 1 year : Progression free survival after 6 months and overall survival after 6 months and one year. [ Time Frame: 1 year ]
|Study Start Date:||June 2010|
|Study Completion Date:||December 2014|
|Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Intracerebral slow continuous infusion of study drug in increasing dose
Biological: delta-24-RGD adenovirus
slow continuous microinfusion in and around the brain tumor during 44 hrs.by 4 temporary placed catheters
Please refer to this study by its ClinicalTrials.gov identifier: NCT01582516
|ERasmus Medical Center|
|Principal Investigator:||Clemens Dirven, MD PhD||Erasmus Medical Center|