Research Project
9251900
? DESCRIPTION (provided by applicant): The Specific Aim of this Phase II SBIR proposal is to develop a catheter-based biosensor for monitoring chemotherapeutic blood levels during drug infusion. This Phase II includes an IDE submission for clinical testing of our device. The ability to monitor blood levels in real-time will facilitate drug dosing within a narrow therapeutic range o minimize toxic side effects (commonly cardiotoxicity) and potentially maximize efficacy. Our initial target therapeutic agent is doxorubicin. Doxorubicin is a commonly used chemotherapeutic whose use is limited by dose-related cardiotoxicity (Swain et al., 2002; Legha et al., 1982). The proposed device allows for monitoring of doxorubicin peak blood levels and cumulative exposure, which are correlated to heart tissue damage (Desoize and Robert, 1994). In part, avoidance of cardiotoxicity is difficult due to inter-individual pharmacokinetic variabiliy - individuals receiving the same dose may have a five-fold variation in area-under- curve (AUC) and peak blood concentrations (Eksborg et al., 1985). Additionally, we will develop a similar imatinib sensor as part of this Phase II proposal as imatinib exposure is highly time dependent and plasma levels are correlated to toxicities (Eechoute et al., 2012; Widmer et al., 2008). In Phase I (1R43HL126473), we demonstrated a catheter-based biosensor for doxorubicin with a physiologically relevant dynamic range of 10nM - 10uM with a stable readout in blood for >8 hours. This device will be inserted into a patient's vein a few minutes prior to a chemo infusion, and will continuously measure drug levels prior to, during, and post infusion. The burdensome existing method of blood draws and lab analysis to monitor patient drug blood levels generally precludes pharmacokinetically guided treatment in a non-research setting. Our device will make individual PK monitoring possible and affordable on a routine basis during drug treatment in most any setting. Studies on pharmacokinetically guided treatment with fluorouracil have demonstrated improved objective response, produced a trend towards higher survival rate, and resulted in fewer grade 3/4 toxicities in metastatic colorectal patients (Gamelin et al., 2008). Th proposed device will allow such monitoring to be routine. In Phase I we showed that we could detect physiologically relevant doxorubicin concentrations for >8 hrs in blood using a prototype of a clinically implementable catheter design for IV fluid delivery. In order to commercialize this product for clinical use, we need to translate our device to a scalable, FDA-compliant manufacturing process and validate sensor functionality in vivo. Success will be determined by demonstrating in vivo sensing for 24 hours in devices manufactured by a process capable of producing 2,600 units/month at $15 per device. The proposed work will culminate in an FDA IDE submission.
