Brain tumors are the second leading cause of cancer-related deaths in people under the age of 20, with Glioblastoma Multiforme (GBM) being the most aggressive and considered incurable with conventional therapies. Irreversible Electroporation (IRE) is a minimally invasive technique invented by Dr. Rafael Davalos (Co-PI) for non-thermal, energy-based ablation of inoperable tumors. IRE uses a series of low energy, unipolar pulsed electric fields, which are applied through electrodes (1.5 mm) inserted into the tumor. Drs. Davalos (VoltMed Co-Founder) and Arena (PI; VoltMed Co-Founder) substantially improved the IRE technique by inventing high frequency irreversible electroporation (H-FIRETM), a patented waveform technology that implements bipolar bursts of electrical energy with individual pulse durations that are two orders of magnitude shorter (? 2 ?s) than those in IRE. H-FIRE? improves the safety of IRE procedures and enables non-thermal ablation of GBM. We have demonstrated that H-FIRETM, unlike IRE, can be performed without the need for neuroparalytics, is more predictable by mitigating tissue heterogeneities, and produces tumor cell-specific ablation. Additionally, H-FIRETM can transiently disrupt the BBB beyond the tumor margin, enabling effective and precise delivery of molecules that are normally blocked from entry by the BBB. H-FIRETM can be used to ablate the bulk of GBM tumors as well as infiltrative cells beyond the tumor margin under MRI guidance. In the current proposal, we will develop the H-FIRETM technology through Phase 1 preclinical studies (following industry-standard FDA Design Controls), culminating in the submission of an IDE proposal to the FDA.
The Specific Aims of this Phase 1 SBIR application are:
Specific Aim 1 : Finalize concept and design for construction of design-control MRI-compatible electrode prototypes for H-FIRETM device. Milestones: (1A) Fabricate an IDE H-FIRETM system that can produce 3000V, 1s biphasic pulses as well as an MRI-compatible probe, (1B) Verify and validate device functionality, in support of IDE/510(k) submission.
Specific Aim 2 : Conduct a proof-of-concept study to determine the safety and efficacy of H-FIRE? in vivo, in canine patients. Milestones: (2A) Demonstrate that H-FIRE? is safe when used in vivo, and (2B) Demonstrate that H-FIRETM is efficacious in the treatment of tumor in vivo. Successful completion of the proposed studies will lead to the development of an IDE device which can be tested in early feasibility human studies to treat GBM. The resulting data will be used to design clinical trials for safety and efficacy in support of our planned regulatory 510(k) submission to the FDA, with the long-term goal of market commercialization.
Brain tumors are the second leading cause of cancer-related deaths in people under the age of 20, with Glioblastoma Multiforme being the most aggressive and considered incurable with conventional therapies. H- FIRETM is a patented waveform technology that implements short (? 2 ?s) bipolar bursts of electrical energy with individual pulse durations, and can be performed without the need for neuroparalytics, is more predictable by mitigating tissue heterogeneities, and produces tumor cell-specific ablation. In the current proposal, we will develop the H-FIRETM technology through Phase 1 preclinical studies (following industry-standard FDA Design Controls), culminating in the submission of an IDE proposal to the FDA, with the long-term goal of testing in early feasibility human studies to treat GBM.
