Intravenous dosing of drugs for applications ranging from cancer chemotherapy to anti-microbials to lytic (blood clot dissolving) agents is limited by systemic toxicity. Currently, the only ways to remove drugs from the blood are through natural metabolism or costly impractical measures such as dialysis. Despite intense focus on targeted drug delivery agents, these therapies are costly and rare, especially considering traditional older drugs are low-cost yet clinically effective, and can be used in a targeted manner with higher efficacy if they could be filtered out of the body after their effect in order to prevent toxicities. Intra-arterial chemotherapy (IAC) is performed in interventional radiology (IR), enabling direct delivery of chemotherapy to tumors by guiding micro-catheters into the arteries feeding these tumors. IAC with Doxorubicin (Dox) has proven to be a successful method demonstrating mortality benefit in randomized controlled trials (1, 2) for treating non- operative primary liver cancer, the third leading cause of cancer deaths worldwide, due to its ability to maximize drug dosage to tumor while limiting systemic dose and toxicity. Nonetheless, up to 50% of the chemo in IAC escapes the tumor and causes toxicity, such as heart failure, thereby limiting high-dose Dox therapy. Dialysis-style filtration has been shown to increase tumor response and long term remission with limited toxicity (3-7), but this method is unsafe, costly, and time consuming. We propose the use of ChemoFilter, a catheter filtration device that would be percutaneously placed similar to a central line under x-ray guidance within the vein draining the organ undergoing IAC in order to capture this escaping chemotherapy from the bloodstream via chemical binding mechanisms. The device would be removed from the patient within 60 minutes (no implant) at the end of the IAC procedure. In this Phase I STTR proposal, we seek to validate ChemoFilter in-vivo. We have demonstrated in-vitro proof-of-concept with our benchtop flow model resulting in Provisional U.S. Patents, and functional catheter prototypes, which are ready to be tested in a swine animal model (IACUC approved, n=24) simulating hepatic IAC. We will demonstrate that in-vivo the ChemoFilter catheter will be: (a) efficacious in rapid, high-capacity binding of Dox from the bloodstream (Specific Aim 1), (b) safely deployed and biocompatible (Specific Aim 2), and (c) able to reduce short-term toxicities (Specific Aim 3). Achievement of these specific aims will lead to FDA 510(k) approval for ChemoFilter as an effective, low-cost, minimally invasive, disposable catheter device that could enable chemotherapy toxicity reduction and high-dose treatments in humans, which will be validated in a Phase II STTR study. ChemoFilter ultimately will lead to a new paradigm in drug therapy as a platform technology for potentially any drug-disease combination (both oncologic and non-oncologic) treated by intra- arterial or even intravenous routes. ! !
Cancer is currently the second leading cause of death in the United States and on track to become the leading cause of death in Westernized nations. Currently, cancer fighting drugs such as chemotherapy can only be removed from the blood through natural metabolism or dialysis, which is unsafe and impractical. The next paradigm shift in cancer therapy is ChemoFilter - a catheter medical device that could be readily inserted into the veins of the body to directly filter drugs, such as chemotherapy, out of the blood stream after these drugs have had their effect on the tumor. ChemoFilter would help patients fight cancer by minimizing drug toxicity and allowing for high-dose therapy to better treat cancer and improve patient survival. Patients suffering from liver cancer, the third leading cause of cancer-death worldwide, and the fastest rising fatal cancer in the U.S. would be the first to benefit from ChemoFilter by as early as 2015. !