Pilot study of an implantable microdevice to test multiple drug responses in prostate cancer patients

植入式微型装置的初步研究，用于测试前列腺癌患者的多种药物反应

• 批准号: 9884746
• 负责人: Nobuhiko Hata
• 金额: $ 67.54万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-04 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9884746
• 关键词: Androgens; Biological Markers; Biology; Biomedical Engineering; Biopsy; Cancer Patient; Cessation of life; Characteristics; Clinical; Clinical Research; Devices; Disease; Dose; Drug Combinations; Drug Exposure; Drug Kinetics; Effectiveness; Ensure; Environment; Foundations; Genetic; Genomics; Gland; Goals; Head; Heterogeneity; Histopathology; Hospitals; Hour; Image; Immune response; Immunologic Markers; Immunologics; Implant; Individual; Lesion; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of prostate; Mass Spectrum Analysis; Measurement; Measures; Medical; Metastatic Prostate Cancer; Methods; Multimodal Imaging; Needle biopsy procedure; Neoadjuvant Therapy; Oncology; Operative Surgical Procedures; Pathology; Pathway interactions; Patients; Pharmaceutical Preparations; Pharmacodynamics; Pharmacologic Actions; Phenotype; Physiological; Pilot Projects; Prediction of Response to Therapy; Procedures; Prostate; Prostate Cancer therapy; Prostatic Neoplasms; Radical Prostatectomy; Regimen; Research; Research Personnel; Resistance; Resources; Retrieval; Role; Safety; Selection for Treatments; Specimen; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Systemic Therapy; Technology; Testing; Tissues; Toxic effect; Translating; Treatment Protocols; Tumor Markers; United States; Urology; Woman; Work; cancer care; chemotherapy; clinically relevant; deprivation; drug response prediction; high risk; image guided; implantation; in vivo; individual patient; individualized medicine; innovation; men; metabolomics; microdevice; minimally invasive; novel; novel therapeutics; optimal treatments; pilot trial; potential biomarker; predicting response; prostate cancer risk; prostate lesions; response; response biomarker; standard of care; systemic toxicity; targeted treatment; tissue biomarkers; transcriptome sequencing; transcriptomics; treatment response; treatment strategy; tumor; tumor heterogeneity

Prostate cancer is the 2nd most common form of cancer among men in United States, in fact, over 26,000 men will die from PCa in the US in 2017. Researchers now believe that prostate cancer specific progression to death can be altered by a more optimal initial treatment strategy that includes systemic treatment. However, there is a paucity of material and research available to optimize the sequence or optimal combination(s) of agents and to maximize the impact of neoadjuvant treatment tailored specifically to the individual patient. This issue is heightened by the recent introduction of new drugs for androgen deprivation, chemotherapy and more recently, targeted therapy of high-risk prostate cancer (PCa). Our long-term goal is to develop an innovative treatment regimen for men with high-risk PCa to treat occult metastatic disease as well as the local tumor, by utilizing neoadjuvant therapy. The objective of this project is to assess the feasibility of implantable microdevices (IMD) to measure local intratumor response to multiple agents. The rationale of the study is that, upon successful completion of this study, we will have shown that we can obtain intratumor efficacy readouts for 19 therapies from a single patient. We will also have established whether these measurements can be used to tailor personalized and specific systemic therapy for a particular patient. With expertise in bioengineering, imaging, pathology, oncology and urology, our team is well prepared to complete this research. We will achieve our goals in the following four specific aims: 1) Develop and clinically validate a device to measure intratumor response to multiple therapies without exposing patients to systemic toxicity; and 2) Demonstrate differential local tumor response to different drugs delivered by IMD; and 3) Examine the role of biomarkers in the treatment response; and 4) To retrieve implanted IMD under MRI guidance using a retrieval device. The proposed research is significant since each tumor responds differently to different agents and lays the foundation for an IMD directed neoadjuvant trial. This will lay the ground work to prove that local intratumor response to micro doses of multiple agents can be used to effectively screen for and tailor the optimal treatment in a novel neo-adjuvant regimen. In addition, by examining the tumor for genetic and physiologic changes, we will be able to in vivo correlate potential biomarkers of tumor response to multiple drugs. Our approach is innovative as the assessment of response occurs within the patient native tumor environment - as such stroma and systemic immune response can be assessed. We will leverage expertise in a precision image guided approach to achieve precise implantation of IMDs into prostate tumors under MRI guidance, and subsequent retrieval during planned surgery.

前列腺癌是美国男性中第二常见的癌症，事实上，超过26000名男性将 2017年在美国死于PCA。研究人员现在认为，前列腺癌的特定进展可以导致死亡 被包括系统治疗在内的更优化的初始治疗策略所改变。然而，有一种稀缺的 可用来优化代理人序列或最佳组合的材料和研究(S)，并使 针对个别患者量身定制的新辅助治疗的影响。这一问题因最近的 用于雄激素剥夺、化疗和最近针对高危人群的靶向治疗的新药推出 前列腺癌(PCa)。我们的长期目标是为患有高危前列腺癌的男性开发一种创新的治疗方案 利用新辅助治疗，治疗隐匿性转移性疾病和局部肿瘤。这样做的目的是 项目是评估植入性微设备(IMD)测量局部肿瘤内对多个 探员们。这项研究的理论基础是，在这项研究成功完成后，我们将证明我们可以 从一名患者那里获得19种治疗方法的肿瘤内疗效读数。我们还将确定这些是否 测量可用于为特定患者量身定做个性化和特定的系统治疗。拥有专业知识 在生物工程、成像、病理学、肿瘤学和泌尿学方面，我们的团队已经做好了完成这项研究的充分准备。我们 将在以下四个具体目标中实现我们的目标：1)开发并在临床上验证测量设备 肿瘤内对多种疗法的反应，而不会使患者暴露于全身毒性；以及2)证明 通过IMD传递的不同药物对局部肿瘤的不同反应；以及3)检查生物标记物在 治疗反应；以及4)在MRI引导下使用检索装置检索植入的IMD。建议数 研究意义重大，因为每种肿瘤对不同的药物有不同的反应，并为IMD奠定基础 定向新辅助试验。这将奠定基础，以证明局部肿瘤内对微剂量 可以使用多种药物来有效地筛选和定制新辅助方案中的最佳治疗方案。 此外，通过检查肿瘤的遗传和生理变化，我们将能够在体内关联潜在的 肿瘤对多种药物反应的生物标志物。我们的方法是创新的，因为响应的评估发生了 在患者的自然肿瘤环境中，可以评估间质和全身免疫反应。我们 将利用精确图像引导方法的专业知识实现IMD在前列腺内的精确植入 MRI引导下的肿瘤，并在计划的手术中随后取回。