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).

摘要：直接放置在患者肿瘤中的新型可植入微型设备（IMD）可以快速评估 多药原位反应。它们可用于任何实体瘤，提供直接、全面、空间多 同时读取超过 20 种药物的组学读数，有可能超越液体和组织活检生物标志物 能力。然而，目前在肿瘤中放置和取出 IMD 需要高侵入性手术 患者发病率和并发症风险过高。对于大多数癌症患者来说，这些风险是令人望而却步的， 因此，正在进行的首次人体 IMD 试验的入组人数有限。 我们开发了一种完全介入（微创）非手术方法来放置和检索 IMD。我们使用定制的针活检设备和图像引导来仅输送和精确去除 IMD 和邻近的药物暴露组织。这是一个简单的门诊手术，类似于常规经皮肿瘤 使用单个微小（<2mm）皮肤切口进行活检。它降低了 IMD 使用的发病率和风险，并且 大大增加当前和未来临床 IMD 试验的入组人数。然而，一项针对动物的临床前研究 在首次使用之前需要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。 该提案描述了兔后肢肿瘤模型的临床前研究，该模型密切模拟了 典型的软组织肉瘤环境，具有以下具体目标：1）确定我们的技术可行性 IMD 放置和取出的介入（非手术）方法； 2) 确定总体安全性和 该同一介入方法的不良事件发生率。介入性 IMD 放置和取出程序 将在由 15 只兔子组成的统计有力的队列中进行。技术可行性和安全终点将 进行评估，并用于为进一步的方法改进和最终的首次人体试验提供信息。 拟议的研究具有创新性，因为它将开发和验证用于个性化治疗的新干预工具 癌症治疗可以作为下一代肿瘤活检。这很重要，因为它将直接启用 一项首次人体试验，旨在评估晚期软组织肉瘤患者基于 IMD 的药物优化。它 还将使更多人参与其他类似或风险较低的解剖区域正在进行的 IMD 临床试验 （例如乳房）。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个肿瘤学 患有经皮可触及肿瘤的患者（类似于常规经皮组织活检）。