TOPIC 345: PREDICTIVE BIOMARKERS OF PROSTATE CANCER PATIENT SENSITIVITY FOR RADIATION LATE EFFECTS

为了实现开发“放射治疗不良反应的预测性生物标志物”的目标，我们建议对I期SBIR工作中开发的产品（“代谢物面板试剂盒”）进行多中心分析验证。将在三个独立的、地理上分布的检测实验室中检测接受SBRT治疗前列腺癌的患者定义队列的血浆代谢物分析结果的精密度、准确度和重现性。将分发从前列腺癌患者获得的临床样本和掺有已知量代谢物的样本，用于Shuttle代谢物“试剂盒”的分析验证。在I期研究中获得的数据已经确定了可能用作辐射迟发效应预测生物标志物的代谢物组。在此，我们提出三个技术目标： 1.生产500个代谢物检测组“试剂盒”和分析软件 2.在三个独立的研究中心测试和验证套件和软件的性能， 3.在监管顾问和FDA输入的协助下，设计一项扩展的多机构验证临床试验，以测试代谢物检测组试剂盒是否可用作临床应用的潜在“代谢物生物标志物”。 在前列腺癌患者中证明原理可能支持代谢物生物标志物产品的开发和商业化。

To address the goals of developing "predictive biomarkers of adverse reactions to radiation treatment", we propose to perform a multi-site analytic validation of the product ("metabolite panel kit") developed in the Phase I SBIR effort. Results of plasma metabolite analysis in defined cohorts of patients treated with SBRT for prostate cancer will be tested for precision , accuracy and reproducibility in three independent, geographically distributed testing laboratories. Clinical samples obtained from patients with prostate cancers and samples spiked with known quantities of metabolites will be distributed for analytic validation of Shuttle's metabolite "kit". The data derived in the Phase I effort have defined metabolite panels for potential use as predictive biomarkers of radiation late effects. here, we propose three technical objectives: 1. To manufacture 500 metabolite panel "kits" and analysis software 2. Test and validate the performance of kits and software at three independent sites and 3. With the assistance of regulatory consultant and FDA input, design an expanded multi institutional validation clinical trial to test the metabolite panel kit for use as a potential "metabolite biomarker" for clinical application. Demonstration of proof of principle in patients with prostate cancer may support development and commercialization of the metabolite biomarker product.