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的微型设备（IMD）可以迅速评估 多药响应原位。它们可以在任何实体瘤中使用，以提供直接，全面的空间多 同时对> 20种药物的杂物读数，并且有可能蚀液体和组织活检生物标志物 功能。但是，将IMD放在目前需要高度侵入性手术中 患者的发病率过高和并发症风险。对于大多数癌症患者，这些风险是高度的， 因此，正在进行的人类IMD试验的入学人数有限。 我们已经开发了一种完全介入的（微创）非手术方法来取回和检索 IMD。我们使用定制的针头活检设备和图像指导来交付和精确删除IMD 和邻近的药物暴露组织。这是一个类似于常规经皮肿瘤的简单门诊手术 活检，使用单个微小（<2mm）的皮肤切口。它降低了IMD使用的发病率和风险，将 大大增加了当前和将来的临床IMD试验的入学率。但是，动物的临床前研究 需要模型来证明此介入方法的技术可行性和安全性 人使用。 该提案描述了兔后肢肿瘤模型中的一项临床前研究，该模型紧密模拟了 典型的软组织肉瘤设置，具有以下特定目的：1）确定我们的技术可行性 介入（非手术）方法的IMD置换和检索方法； 2）确定总体安全性和 同一介入方法的不良事件率。介入的IMD放置和检索程序 将以15只兔子的统计动力队列进行。技术可行性和安全终点将是 经过评估，并用于为进一步的方法提供信息，并最终是人类试验。 拟议的研究具有创新性，因为它将开发并验证新的介入工具以进行个性化 可以作为下一代肿瘤活检的癌症治疗。它很重要，因为它将直接启用 第一次人类试验，用于评估晚期软组织肉瘤患者的基于IMD的药物优化。它 还将在其他类似或较低风险的解剖区域进行正在进行的IMD临床试验的入学人数。 （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，此处开发的介入方法可能适用于每种肿瘤学 患有经皮肿瘤的患者（类似于常规经皮组织活检）。