Optimizing Ultrasound Enhanced Delivery of Therapeutics

优化超声增强治疗的输送

• 批准号: 9337418
• 负责人: Flemming Forsberg
• 金额: $ 62.44万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-25 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9337418
• 关键词: Academic Medical Centers; Acoustics; Address; Adjuvant; Animals; Biodistribution; Biological; Cancer Etiology; Cell Line; Cessation of life; Clinic; Clinical; Clinical Trials; Contrast Media; Custom; Data; Development; Diagnostic; Disease; Drug Delivery Systems; Eastern Cooperative Oncology Group; Effectiveness; Enrollment; Environment; Equipment; Excision; Goals; Human; Image Enhancement; Immunohistochemistry; In Vitro; Industrialization; Institutes; Israel; Lead; Leadership; Liver; Malignant neoplasm of pancreas; Mediating; Medical; Methodology; Methods; Microbubbles; Monitor; Multi-Institutional Clinical Trial; Operative Surgical Procedures; Organ; Outcome; Pancreas; Pancreatic Adenocarcinoma; Pancreatic Ductal Adenocarcinoma; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Pharmacotherapy; Pre-Clinical Model; Protocols documentation; Publishing; Radiation; Research; Research Personnel; Solid Neoplasm; Survival Rate; System; Systemic Therapy; Techniques; Technology; Therapeutic; Translating; Tumor Volume; Ultrasonography; United States; Universities; University Hospitals; Unresectable; Woman; X-Ray Computed Tomography; base; cancer diagnosis; chemotherapy; clinical investigation; clinical practice; clinically translatable; contrast enhanced; design; human study; image-guided drug delivery; imaging modality; imaging platform; improved; improved outcome; innovation; men; mouse model; multidisciplinary; new therapeutic target; novel; pre-clinical research; programs; quantitative imaging; quantitative ultrasound; standard of care; tool; treatment response

Abstract Pancreatic cancer is the third most common cancer diagnosed in the United States, with more than 43,000 new cases in 2013. It is the fourth leading cause of cancer-related death in both men and women. Nonetheless, there has been no significant improvement in survival for pancreatic ductal adenocarci- noma (PDAC) patients over the past 30+ years. For this reason, there is a considerable and urgent clinical need to develop innovative strategies for effective drug delivery and treatment monitoring, re- sulting in improved outcomes for patients with PDAC. Our proposal aims at developing contrast-enhanced ultrasound-mediated image-guided drug delivery (CEUS-IGDD) to be that methodology and to translate it from the lab to the clinic. The specific tasks are designed to improve the understanding and methodology for control and monitoring of this IGDD platform, with an initial clinical focus on enhancing the effectiveness of standard chemotherapeutics for treatment of inoperable PDAC. Inherently this project constitutes a multidisciplinary challenge (technological, biological, physical, and medical), and our strategy to address the critical barriers therefore unites an interdisciplinary team of academic and industrial investigators from GE Global Research (GE), Haukeland University Hospital and University of Bergen (together: Bergen), Thomas Jefferson University (TJU), and Rush University Medical Center with more limited efforts by the Israel Institute of Technology and GlaxoSmithKline (GSK). Aim 1 will develop tools and methods to ascertain optimal conditions (acoustic regime, bubble type) for maximum drug delivery with minimal application of diagnostic-range acoustic energy. Aim 2 utilizes two com- plementary established pancreatic adenocarcinoma mouse models, using human MIA PaCa-2luc (Bergen) and PANC-1 (TJU) cell lines. The efficacy of CEUS-IGDD will be evaluated using biodistribution data and quan- titative imaging methods to monitor treatment response expecting a greater median survival of at least 5 days and a median tumor volume reduction of 50% in the treated group compared to animals receiving drug alone. The main focus of this proposal is Aim 3, where a three year, multi-center clinical trial en- rolling one hundred and twenty (120) patients with metastatic or locally advanced and surgically unresectable PDAC will be conducted at TJU and Bergen. All patients will undergo standard of care chemotherapy, with one-half receiving adjunctive CEUS-IGDD. Patient outcomes will be compared by quantitative ultrasound as- sessment, CT imaging including RECIST criteria, ECOG grade, and immunohistochemistry to assess local progression-free and overall survival with the main endpoint being to increase the number of chemo- therapy cycles by 75% in the IGDD group relative to controls.

摘要