Interventional method development for multiplexed personalized drug evaluation using implantable microdevices

使用植入式微型设备进行多重个性化药物评估的介入方法开发

• 批准号: 10727646
• 负责人: Sharath Bhagavatula
• 金额: $ 7.69万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-25 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10727646
• 关键词: Adverse event; Affect; Anatomy; Animal Model; Animals; Antineoplastic Agents; Biological Markers; Biopsy; Breast; Cancer Patient; Cause of Death; Cell Death; Clinical; Clinical Trials; Complication; Custom; Data; Device Designs; Device Removal; Devices; Dose; Drug Combinations; Drug Evaluation; Drug Exposure; Drug toxicity; Effectiveness; Enrollment; Environment; Evaluation; Excision; Feasibility Studies; Future; Goals; Hemorrhage; Hindlimb; Human; Implant; In Situ; Injury; Intervention; Interventional radiology; Liquid substance; Methods; Modeling; Morbidity - disease rate; Needle biopsy procedure; Oncology; Operative Surgical Procedures; Oryctolagus cuniculus; Outcome; Outpatients; Patients; Pharmaceutical Preparations; Pharmacotherapy; Procedures; Radiology Specialty; Regional Anatomy; Reproducibility; Research; Retrieval; Risk; Safety; Serum Markers; Skin; Soft tissue sarcoma; Solid Neoplasm; Specimen; Structure; Surgical incisions; Techniques; Technology; Testing; Tissues; Tumor Debulking; Tumor Tissue; Work; cancer imaging; cancer therapy; clinical translation; cohort; effective therapy; first-in-human; image guided; implantation; improved; innovation; method development; microdevice; miniaturized device; minimally invasive; mouse model; multiple omics; next generation; novel; personalized cancer therapy; personalized medicine; personalized strategies; precision drugs; preclinical study; predicting response; prototype; response; safety and feasibility; tool; treatment optimization; treatment strategy; tumor

Abstract: Novel implantable miniaturized devices (IMDs) placed directly in patient tumors can rapidly evaluate multi-drug responses in-situ. They can be used in any solid tumor to provide direct, comprehensive, spatial multi- omic readouts of >20 drugs simultaneously, with potential to eclipse liquid and tissue biopsy biomarker capabilities. However, placing and retrieving IMDs in tumors currently requires highly invasive surgery with excessively high patient morbidity and complication risks. For most cancer patients, these risks are prohibitive, and as a result ongoing first-in-human IMD trials have had limited enrollment. We have developed a fully interventional (minimally invasive) non-surgical method to place and retrieve IMDs. We use custom needle biopsy devices and image guidance to deliver and precisely remove only the IMD and adjacent drug-exposed tissue. This is a simple outpatient procedure similar to routine percutaneous tumor biopsies, using a single tiny (<2mm) skin incision. It reduces the morbidity and risks of IMD use, and would greatly increase enrollment in current and future clinical IMD trials. However, a preclinical study in an animal model is needed to demonstrate technical feasibility and safety of this interventional method prior to first-in- human use. This proposal describes a preclinical study in a rabbit hindlimb tumor model that closely simulates a typical soft tissue sarcoma setting, with the following specific aims: 1) determine the technical feasibility of our interventional (non-surgical) approach for IMD-placement and retrieval; and 2) determine the overall safety and adverse event rate of this same interventional method. Interventional IMD placement and retrieval procedures will be performed in a statistically-powered cohort of 15 rabbits. Technical feasibility and safety endpoints will be assessed, and used to inform further method refinement and ultimately first-in-human trials. The proposed study is innovative as it will develop and validate new interventional tools for personalized cancer treatment that could serve as the next generation of tumor biopsy. It is significant as it will directly enable a first-in-human trial to evaluate IMD-based drug optimization in patients with advanced soft tissue sarcomas. It will also enable greater enrollment in ongoing IMD clinical trials in other similar or lower risk anatomic regions (e.g. breast). Ultimately, if the overall long-term goal of clinically validating IMD-based personalized treatment optimization is achieved, the interventional methods developed here could be applicable to every oncology patient with a percutaneously accessible tumor (similar to routine percutaneous tissue biopsies).

翻译后摘要：新型植入式微型设备（IMD）直接放置在病人的肿瘤可以快速评估 多种药物原位反应。它们可用于任何实体瘤，以提供直接、全面、空间多方位的治疗。 同时读取>20种药物的组学数据，有可能超越液体和组织活检生物标志物 能力的然而，在肿瘤中放置和取回IMD目前需要高度侵入性的手术， 过高的患者发病率和并发症风险。对于大多数癌症患者来说，这些风险是禁止的， 因此，正在进行的首次人体IMD试验的招募人数有限。 我们已经开发了一种完全介入（微创）的非手术方法来放置和取回 IMD。我们使用定制的穿刺活检设备和图像引导来输送和精确地移除IMD 和邻近的药物暴露组织。这是一个简单的门诊程序类似于常规经皮肿瘤 活检，使用单个微小（<2 mm）皮肤切口。它降低了IMD使用的发病率和风险， 大大增加了当前和未来IMD临床试验的入组人数。然而，一项动物临床前研究 需要一个模型来证明这种介入方法的技术可行性和安全性， 人类使用。 该提案描述了一项在兔后肢肿瘤模型中进行的临床前研究， 典型的软组织肉瘤设置，具有以下具体目标：1）确定我们的技术可行性 植入和取出IMD的介入（非手术）方法; 2）确定总体安全性， 不良事件发生率。介入IMD放置和回收程序 将在15只家兔的自动动力队列中进行。技术可行性和安全性终点将 评估，并用于进一步的方法改进和最终的首次人体试验。 拟议的研究是创新的，因为它将开发和验证新的介入工具， 可以作为下一代肿瘤活检的癌症治疗方法。它的意义重大，因为它将直接使 一项首次在人体试验，以评估基于IMD的药物优化在晚期软组织肉瘤患者中的应用。它 还将使更多的人能够在其他类似或风险较低的解剖区域中参与正在进行的IMD临床试验 (e.g.乳房）。最终，如果临床验证基于IMD的个性化治疗的总体长期目标 实现了优化，这里开发的介入方法可以适用于每一种肿瘤学 患有经皮可触及肿瘤的患者（类似于常规经皮组织活检）。