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

基本信息

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
项目类别：
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

项目摘要

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大最常见的癌症，事实上，超过 26,000 名男性患有前列腺癌。 2017 年，美国有 1 例患者死于 PCa。研究人员现在认为，前列腺癌特定的死亡进展可能与通过更优化的初始治疗策略（包括全身治疗）进行改变。然而，却有少量可用于优化药物序列或最佳组合并最大化药物效果的材料和研究专门针对个体患者的新辅助治疗的影响。这个问题因最近的事件而变得更加突出引入用于雄激素剥夺、化疗以及最近针对高危人群的靶向治疗的新药前列腺癌（PCa）。我们的长期目标是为患有高危 PCa 的男性开发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以及局部肿瘤。此举的目的该项目旨在评估植入式微型设备（IMD）测量局部肿瘤内对多种物质的反应的可行性代理。这项研究的基本原理是，成功完成这项研究后，我们将证明我们可以获取单个患者 19 种疗法的肿瘤内疗效读数。我们还将确定这些是否测量结果可用于为特定患者量身定制个性化和特定的全身治疗。凭借专业知识在生物工程、影像学、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。我们将实现以下四个具体目标： 1) 开发并临床验证测量设备对多种疗法的肿瘤内反应，而不使患者暴露于全身毒性； 2) 展示局部肿瘤对 IMD 递送的不同药物的不同反应； 3) 检查生物标志物在治疗反应； 4) 使用检索装置在 MRI 引导下检索植入的 IMD。拟议的这项研究意义重大，因为每种肿瘤对不同药物的反应不同，并为 IMD 奠定了基础定向新辅助试验。这将为证明局部肿瘤内对微剂量的反应奠定基础。多种药物可用于有效筛选和定制新型新辅助治疗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。当评估响应时，我们的方法是创新的在患者天然肿瘤环境内 - 因此可以评估基质和全身免疫反应。我们将利用精确图像引导方法的专业知识来实现 IMD 精确植入前列腺 MRI 引导下的肿瘤，以及随后在计划手术期间取出的肿瘤。