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: 10360532
• 负责人: Nobuhiko Hata
• 金额: $ 66.74万
• 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/10360532
• 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; Translating; Treatment Protocols; Treatment-related toxicity; 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种最常见的癌症形式，实际上，超过26,000名男性将 2017年，美国PCA死亡。研究人员现在认为，前列腺癌特异性进展可能是 通过包括全身治疗的最佳初始治疗策略的改变。但是，很少 可用的材料和研究来优化剂的序列或最佳组合，并最大化 新辅助治疗专门针对个体患者的影响。最近的问题加剧了 引入新药用于雄激素剥夺，化学疗法和最近的针对高危治疗 前列腺癌（PCA）。我们的长期目标是为具有高风险PCA的男性开发一种创新的治疗方案 通过利用新辅助治疗来治疗隐匿性转移性疾病和局部肿瘤。这个目的 项目是为了评估可植入的微型发行版（IMD）的可行性，以测量对多个的局部肿瘤内反应 代理商。该研究的理由是，在成功完成这项研究后，我们将表明我们可以 从一名患者那里获得19种疗法的肿瘤内疗效读数。我们还将确定是否 测量可用于针对特定患者量身定制个性化和特定的全身疗法。具有专业知识 在生物工程，成像，病理学，肿瘤学和泌尿外科中，我们的团队已准备好完成这项研究。我们 将在以下四个特定目标中实现我们的目标：1）开发和临床验证设备以测量 肿瘤内对多种疗法的反应，而不会暴露患者全身毒性； 2）演示 局部肿瘤对IMD递送的不同药物的差异反应； 3）检查生物标志物在 治疗反应； 4）使用检索设备在MRI指导下检索植入IMD。提议 研究很重要，因为每个肿瘤对不同的药物的反应都不同，并为IMD奠定了基础 定向新辅助试验。这将奠定地面工作，以证明局部肿瘤内对微剂量的反应 多种药物可用于有效筛选并定制新型新辅助方案中的最佳治疗方法。 另外，通过检查肿瘤的遗传和生理变化，我们将能够体内相关的潜力 肿瘤对多种药物反应的生物标志物。我们的方法是创新的，因为对响应的评估发生了 在患者本地肿瘤环境中 - 可以评估这种基质和全身免疫反应。我们 将通过精确图像指导的方法利用专业知识来实现​​IMD的精确植入前列腺 MRI指导下的肿瘤，并在计划手术期间进行检索。