Comparison of convection enhanced delivery systems in a randomized controlled clinical study of recurrent Grade 3-4 glioma patients

Project Abstract Significance: The devasting outcomes for glioblastoma (GBM) patients remain despite the advances in cancer therapy. Improved GBM therapy as a critical unmet need requires new intervention capabilities and the likely integration of innovative GBM interventions as proposed with this research. The premise of this project is that one of the challenges to improving GBM patient lives can be overcome by increased therapeutic coverage of GBM tumors using an innovative convection enhanced delivery (CED) catheter. Innovations: The proposed SBIR Direct to Phase II research offers the innovations of (1) improved GBM therapeutic agent delivery obtained with the CED Porous Brain Infusion Catheter (PBIC) when combined with a more accurate Molecular Flow Simulations (MFS) software – as the PBIC System and, (2) a novel approach to evaluate CED drug delivery catheters with a randomized controlled trial. Preliminary Data: PBIC has demonstrated preclinical in vivo increased volume of infused brain distribution. The MFS infusion planning software has demonstrated robust correlation of actual and simulated human brain tumor infusions and has obtained FDA 510k marketing clearance. Comparative GBM tumor infusion simulations using the FDA cleared MFS software indicate PBIC can increase therapeutic coverage of GBM tumors. Hypothesis: The PBIC will have equivalent or improved safety profile and significantly greater percentage of enhancing tumor coverage than an end port CED catheter. Overall Project Objective: Accelerate CED research with the clinical safety and infusion distribution evaluation of the PBIC System in Aim 1 research. Specific Aim 1: First-In-Human study to evaluate PBIC safety and recurrent GBM tumor infusion distribution efficacy. CreoSalus will manufacture PBIC test devices and provide physician placement training. Duke investigators with Therataxis support will evaluate the PBIC to treat recurrent WHO grade 3 or 4 malignant glioma (rGBM) patients, using an existing Duke clinical trial of intratumoral therapeutic infusion via CED of D2C7-IT and 2141-V11 (NCT04547777, IND 151390). A total of 24 patients (12 patients per catheter group) will be randomized to either the PBIC or the current Duke CED end port catheter. Safety analysis will be based on catheter related adverse events. Infusion distribution in enhancing tumor will be evaluated with co-infused PET imaging tracers (124I-human serum albumin (HSA)) same as used in prior Duke Brain Tumor Center and Therataxis CED distribution studies. Aim 1 Milestone: Compared to the control end port catheter the PBIC will demonstrate (a) equivalent or better safety and (b) significantly improved (p<.05) 124I-HSA distribution in enhancing tumor. Research Impact: Improved drug distribution using a catheter specifically designed for CED to improve GBM and other brain disease/injury patient outcomes.