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

为了达到开发“放射治疗不良反应的预测生物标志物”的目标，我们建议对在第一阶段SBIR工作中开发的产品(“代谢物面板试剂盒”)进行多点分析验证。前列腺癌患者接受SBRT治疗的特定队列中的血浆代谢物分析结果将在三个独立的、地理分布的测试实验室进行精密度、准确性和重复性测试。从前列腺癌患者身上获得的临床样本和添加了已知数量的代谢物的样本将被分发，用于对Shuttle的代谢物“试剂盒”进行分析验证。在第一阶段工作中获得的数据已经确定了代谢物面板，可能用作辐射延迟效应的预测生物标记物。在这里，我们提出三个技术目标： 1.制作500个代谢物面板“试剂盒”和分析软件 2.在三个独立的站点测试和验证套件和软件的性能 3.在监管顾问和FDA投入的协助下，设计一项扩大的多机构验证临床试验，以测试代谢物试剂盒作为潜在的临床应用的“代谢物生物标志物”。前列腺癌患者的原则证明可能支持代谢物生物标记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.