Clinical biomarker for early prediction of chemotherapy-induced peripheral neuropathy

Project Summary / Abstract Chemotherapy induced peripheral neuropathy (CIPN) is a major side effect of oxaliplatin, a key drug in 1st line regimens for treating colorectal cancer. Dose-limiting CIPN prevents rt25% of patients from receiving full, maximally effective dose of oxaliplatin. In addition, 10-40% of patients receiving oxaliplatin-based therapy for colorectal cancer with develop chronic CIPN, which is painful, impairs quality of life, and is associated with higher opioid use rates. Approaches for CIPN prevention have not yielded meaningful success. A biomarker that can help with early prediction of CIPN will be a major facilitator of shared decision making (i.e. changing chemotherapy intensity, frequency, or type) to prevent CIPN, and in stratifying patients to targeted clinical trials for CIPN prevention. To that end, we have recently characterized the Allo-ColdTM method for early prediction of CIPN, based on dynamic quantification of cold hypersensitivity. In preliminary studies, the method demonstrated promising sensitivity and specificity. It is non-invasive, scalable, and has a potential to be readily implementable, including in low-resource settings. Our main goal for this Phase I STTR proposal is to develop and test a user-centered mobile health system prototype for collecting, storing, aggregating and processing patient-reported data on palmar cold sensitivity to predict CIPN. In Aim 1, we will develop the Allo-Cold mobile health technology prototype using a user-centered design approach. We will use three-tier architecture to develop the patient user interface, data management and storage, and data logic components of a mobile app for CIPN risk prediction. We will iteratively test and refine the prototype. We will conduct interviews with cancer patients for feedback on prototype acceptability, and with clinicians to assess implementation barriers. In Aim 2, we will demonstrate adherence and predictive performance of Allo-Cold system in patients undergoing oxaliplatin-based chemotherapy. Twenty-four patients with stage III/IV colorectal cancer undergoing oxaliplatin-based therapy will use Allo-Cold, and self-report cold pain and cold unpleasantness daily for 10 weeks (5 cycles) of chemotherapy. We will determine patient adherence and the performance of our predictive algorithm in predicting dose-limiting CIPN. In this Phase I STTR proposal, we expect to determine the feasibility of the Allo-Cold system by confirming its usability, adherence, and predictive performance in the context of oxaliplatin-based therapy for colorectal cancer. Phase II STTR proposal will focus on completing full clinical and analytical validation of Allo-Cold as a predictive biomarker for CIPN, toward FDA approval and subsequent commercialization.