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.

Grant Number: 5R44CA295197-02
NIH Institute/Center: NIH
Principal Investigator: Vasiliy Abramov