Clinical Evaluation of an Implantable Lab-in-a-patient microdevice that measures in-situ response to therapies in advanced ovarian cancer

用于测量晚期卵巢癌治疗原位反应的可植入患者实验室微装置的临床评估

• 批准号: 9623339
• 负责人: Oliver Jonas
• 金额: $ 21.52万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-08 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9623339
• 关键词: Abdomen; BRCA1 gene; Biological Markers; Biopsy; Cancer Etiology; Cancer Patient; Cessation of life; Characteristics; Clinical; Clinical Research; Clinical Treatment; Clinical Trials; Data; Data Set; Devices; Disease; Disease Resistance; Dose; Drug Combinations; Drug Exposure; Drug Screening; Effectiveness; Engineering; Excision; Feasibility Studies; Foundations; Future; Genomics; Genotype; Head; Heterogeneity; Hour; Immune; Immunologic Markers; Implant; In Situ; Interventional radiology; Lesion; Location; MAP Kinase Gene; Malignant neoplasm of ovary; Measurement; Measures; Medical; Methods; Needle biopsy procedure; Neoplasm Metastasis; Operative Surgical Procedures; Outcome; Patients; Pharmaceutical Preparations; Pharmacodynamics; Phenotype; Platinum; Prediction of Response to Therapy; Predictive Value; Procedures; Refractory; Relapse; Research; Resistance; Safety; Selection for Treatments; Serous; Technology; Testing; Time; Tissues; Toxic effect; Translating; Tumor Debulking; United States; Vascular Endothelial Growth Factors; Woman; Work; biomarker identification; cancer care; chemotherapy; cytotoxic; drug efficacy; drug response prediction; implantation; in vivo; individual patient; microdevice; miniaturize; minimally invasive; novel; optimal treatments; patient population; phenotypic biomarker; pilot trial; pre-clinical; predicting response; predictive marker; relapse patients; research clinical testing; response; response biomarker; safety and feasibility; standard of care; systemic toxicity; taxane; tissue biomarkers; transcriptomics; treatment planning; tumor; tumor heterogeneity; tumor microenvironment

Project summary: Ovarian cancer (OC) is a leading cause of cancer deaths in women in the United States. The clinical treatment of OC is marked by high initial response rates to 1st line standard-of-care (SOC) platinum/taxane treatment, but also significant relapse rates. A major unmeet need in this disease exists to identify optimal 2nd line therapy options in the platinum resistant or refractory setting which yield superior outcomes compared with current treatment selection which is largely empirical. Many single and combination agents are currently in use or in clinical trials as 2nd line treatments for OC, but there are few reliable biomarkers available to predict response to these various types of cytotoxic or targeted chemotherapies. Recent studies have identified potential genomic and other markers, including BRCA1/2, VEGF, MAPK, PI3K and others. Advances in biomarker identification, however, are slow because each trial only administers a single therapy on every patient at a given time, and thus only allows biomarker/phenotype correlations on one therapy at a given tumor state. We have developed a technology that allows us to measure the phenotypic effect of a large number of distinct agents or drug combinations within a single tumor in a rapid and minimally invasive manner and without systemic toxicities. The technology represents a new paradigm for predicting proactively, rather than empirically, the effect of drugs inside a patient tumor. Consisting of implantable microdevices, which release microdoses of up to 120 distinct agents or combinations in parallel into small confined regions of tumor, it allows for direct measurement of drug/tumor interaction using established pharmacodynamic readouts for each therapy tested within the native tumor microenvironment. This proposal seeks to translate the microdevices into clinical use through a pilot trial in ovarian cancer patients. Up to 6 microdevices will be implanted into omental tumors one day prior to surgery where they are expected to provide a rapid and comprehensive snapshot of how the tumor actually responds to all the available therapies. 6 spatially separated readouts from distinct parts of the tumor will also provide a novel functional examination of tumor heterogeneity. All of the readouts will be correlated with genomic, transcriptomic, immune and tissue biomarkers, effectively performing 20 or more biomarker trials in each patient with six-fold replicates, with only one extra biopsy procedure, and at minute drug exposure levels. This unprecedented clinical study seeks to validate safety, usage and procedures for obtaining multiple drug phenotypes from microdevices within patients, and to significantly expand the field's understanding of predictive biomarkers in ovarian cancer. If successful, this research may lay the foundation for application of this drug screening microdevice beyond ovarian cancer.

项目摘要： 卵巢癌（OC）是美国女性癌症死亡的主要原因。临床 OC的治疗以高初始响应率对第一线护理（SOC）铂/紫杉烷的标志 治疗，但也明显的复发率。存在这种疾病的主要不合情可及，以识别最佳 铂或耐火环境中的第二线治疗选择，产生卓越的结果 与当前的治疗选择相比，这在很大程度上是经验的。 许多单一和组合剂目前正在使用或在临床试验中作为第二行处理 对于OC，但是很少有可靠的生物标志物可以预测对这些类型的各种类型的反应 细胞毒性或靶向化疗。最近的研究确定了潜在的基因组和其他标记， 包括BRCA1/2，VEGF，MAPK，PI3K等。但是，生物标志识别的进步是 缓慢，因为每个试验仅在给定时间对每个患者进行一次治疗，因此 允许在给定肿瘤状态下一种疗法上的生物标志物/表型相关性。 我们已经开发了一项技术，使我们能够测量大量的表型效应 在单个肿瘤中以快速而微创的方式进行不同的药物或药物组合， 没有全身毒性。该技术代表了一个新的范式，可以主动预测 从经验上讲，药物在患者肿瘤内的作用。由可植入的微型版本组成， 释放多达120种不同剂或组合的微剂量并联成小小的约束区域 肿瘤，它允许使用已建立的药效学直接测量药物/肿瘤相互作用 在天然肿瘤微环境中测试的每种疗法的读数。 该提案旨在通过卵巢试验试验将微论条件转化为临床使用 癌症患者。在手术前一天，最多可将多达6个微型版本植入肿瘤 预计他们将为肿瘤如何对所有人做出反应提供快速而全面的快照 可用的疗法。 6从肿瘤的不同部分的空间分离的读数也将提供 肿瘤异质性的新功能检查。所有读数将与基因组相关， 转录组，免疫和组织生物标志物，有效地进行20或更多的生物标志物试验 重复六倍的患者，只有一项额外的活检手术，并且在细微的药物暴露水平下。 这项前所未有的临床研究旨在验证获得的安全性，用法和程序 从患者内部微型电视的多种药物表型，并显着扩大了该领域的 了解卵巢癌的预测生物标志物。如果成功，这项研究可能奠定基础 用于应用该药物筛查以外的卵巢癌。

项目成果

Lexicon for renal mass terms at CT and MRI: a consensus of the society of abdominal radiology disease-focused panel on renal cell carcinoma.

• DOI: 10.1007/s00261-020-02644-x
• 发表时间: 2021-03
• 期刊: Abdominal radiology (New York)
• 作者: Shinagare AB;Davenport MS;Park H;Pedrosa I;Remer EM;Chandarana H;Doshi AM;Schieda N;Smith AD;Vikram R;Wang ZJ;Silverman SG
• 通讯作者: Silverman SG