Fluorescein for Sentinel Lymph Node Detection

用于前哨淋巴结检测的荧光素

• 批准号: 8117732
• 负责人: Robert Hans Ingemar Andtbacka
• 金额: $ 100万
• 依托单位: VESTAN, INC.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8117732
• 关键词: Agreement; Am 80; Anaphylaxis; Applications Grants; Area; Back; Breast Melanoma; Canada; Cancer Intervention; Caring; Clinical Trials; Collection; Colloids; Community Hospitals; Detection; Development; Devices; Direct Costs; Dose; Dropout; Drug Formulations; Drug Kinetics; Dyes; Educational Materials; England; Evaluable Disease; Evaluation; Excision; Eyeglasses; Family suidae; Fluorescein; Fluorescence; Fluorescent Dyes; Funding; Geographic Locations; Grant; Health; Health Care Costs; Healthcare; Hispanics; Hospitals; Human; Image; Imagery; Improve Access; Institutes; Institutional Review Boards; Label; Life; Light; Lighting; Location; Lymph Node Mapping; Lymphatic; Lymphatic System; Lymphazurin; Malignant Neoplasms; Maps; Marketing; Medical Device; Medical Imaging; Metabolic Clearance Rate; Methods; Modification; Monitor; Native Americans; Neoplasm Metastasis; Operating Rooms; Operative Surgical Procedures; Outcome; Pamphlets; Patient Care; Patient Education; Patients; Pharmaceutical Preparations; Phase; Phase II Clinical Trials; Pilot Projects; Population; Population Study; Positron-Emission Tomography; Preparation; Primary Neoplasm; Printing; Procedures; Progress Reports; Protocols documentation; Radioactive; Radioisotopes; Recording of previous events; Recruitment Activity; Red-Green Color Blindness; Research; Risk; Rural Hospitals; Sample Size; Sentinel Lymph Node; Sentinel Lymph Node Biopsy; Series; Services; Side; Skin; Small Business Technology Transfer Research; Solutions; Sterility; Sulfur; Surgeon; System; Tattooing; Technetium 99m; Technology; Testing; Time; Toxic effect; Universities; Utah; Visual; animal data; cancer type; cost; drug clearance; experience; improved; instrumentation; intraoperative imaging; lymph nodes; malignant breast neoplasm; melanoma; operation; outreach program; pre-clinical; programs; prototype; public health relevance; research clinical testing; response; stability testing; success; tumor; web site

DESCRIPTION (provided by applicant): In this Phase II STTR project, Vestan Medical Imaging, Inc. will complete the development and clinical evaluation of its proprietary formulation of a fluorescent drug and new medical devices for Sentinel Lymph Node (SLN) biopsy for the surgical treatment of melanoma and breast cancer. Vestan will partner with the University of Utah Huntsman Cancer Institute (HCI) through a Subaward to conduct two Phase I/II clinical trials in patients undergoing a SLN biopsy for malignant melanoma or breast cancer. The FDA has granted IND- exempt status for each trial. Both studies have been reviewed and approved by the Univ. of Utah IRB. HCI and the Univ. of Utah serve a 7-state geographic region that includes UT, MT, ID, WY, eastern NV, western CO, and northern AZ. The geographically large patient service area and outreach programs to Hispanic and nearby Native American population centers enable these hospitals to accrue patients on clinical trials quickly, and with a study population that reflects the ethnic diversity of this large geographic region. The Specific Aims to complete the development and evaluation of this new method of SLN biopsy are: (1) Stability testing of the fluorescent drug formulation and determination of the drug clearance rate through pharmacokinetic studies. (2) Produce a sufficient number of prototype illumination and visualization devices for use in the 2 clinical trials. (3) Conduct two Phase I dose-escalation studies of subdermally- or intradermally-injected 0.001% to 1% fluorescent dye in 20 patients undergoing a SLN biopsy procedure in the treatment of malignant melanoma and in 20 patients undergoing a SLN biopsy procedure for breast cancer. (4) Conduct two statistically-robust Phase II clinical trials of the fluorescent dye and visualization devices in 80 patients undergoing SLN biopsy for malignant melanoma and 80 patients undergoing SLN biopsy for breast cancer. (5) Vestan will develop and disseminate an educational program on the benefits of using a fluorescent dye in SLN biopsy procedures. Most patients with melanoma or breast cancer currently receive a SLN biopsy procedure that employs a non-fluorescent blue dye, Lymphazurin(R) and a Tc-99m-radioactive sulfur colloid preparation. There have been sporadic shortages of Lymphazurin(R) including its complete nationwide unavailablity for 16 months in 2006-07, possibly diminishing the nationwide quality of patient care. Vestan's approach will eliminate the need for Lymphazurin(R), avoid the up to 2% risk of anaphylactic reaction from Lymphazurin(R), eliminate the permanent tattooing of patients by Lymphazurin(R), and allow surgeons with red- green color blindness to achieve better SLN detection rates. Vestan's technology will set the groundwork for other intraoperative fluorescent technologies to lower the cost of healthcare and improve surgical outcomes worldwide, including rural and community hospitals where the access to short-lived radioisotopes for intraoperative use may not exist. PUBLIC HEALTH RELEVANCE: The use of fluorescent drugs for the location and direct visualization of lymph nodes in Sentinel Lymph Node (SLN) biopsy procedures in the operating room can replace non-fluorescent and potentially dangerous blue dyes and short-lived radioisotopes in patients undergoing an operation for breast cancer, malignant melanoma, and other types of cancer that metastasize by way of the lymphatic system. The direct fluorescent visualization technology being developed by Vestan Medical Imaging, Inc. may be superior to the current SLN biopsy procedure that employs a dark-blue dye (Lymphazurin(R)) that has undergone periodic nationwide shortages, including its unavailability for 16 months in 2006-2007, and a Tc-99m-radioactive sulfur colloid preparation. The worldwide availability of Tc-99m from a reactor in Canada or England is also tenuous. Vestan's technology has been developed to lower the cost of healthcare and improve the access to state-of-the-art healthcare worldwide. Vestan's fluorescence technology for SLN biopsy will enable rural and community hospitals that have limited access to short-lived radioisotopes to offer the best-possible surgical care to patients with cancer. Vestan has developed this technology to be inexpensive, high-impact, easy to manufacture, and commercially available within a very short time after completion of clinical trials.

描述（由申请人提供）：在这个二期STTR项目中，Vestan Medical Imaging, Inc.将完成其专利荧光药物配方的开发和临床评估，以及用于黑色素瘤和乳腺癌手术治疗前哨淋巴结（SLN）活检的新型医疗设备。维斯坦将与犹他大学亨茨曼癌症研究所（HCI）通过Subaward合作，在接受恶性黑色素瘤或乳腺癌SLN活检的患者中进行两项I/II期临床试验。美国食品和药物管理局已经授予每个试验IND豁免地位。这两项研究都得到了犹他大学伦理委员会的审查和批准。HCI和犹他大学服务于7个州的地理区域，包括UT， MT， ID， WY， NV东部，CO西部和AZ北部。地理上庞大的患者服务区域和向西班牙裔和附近的美洲原住民人口中心的推广项目使这些医院能够快速积累临床试验患者，并且研究人群反映了这一大地理区域的种族多样性。完成这种SLN活检新方法的开发和评价的具体目的是：(1)通过药代动力学研究进行荧光药物制剂的稳定性试验和药物清除率测定。(2)生产足够数量的原型照明和可视化设备，用于2个临床试验。(3)对20例接受恶性黑色素瘤SLN活检的患者和20例接受乳腺癌SLN活检的患者进行皮下或皮内注射0.001%至1%荧光染料的两项I期剂量递增研究。(4)在80例恶性黑色素瘤SLN活检患者和80例乳腺癌SLN活检患者中进行两项统计稳健性的荧光染料和可视化装置的II期临床试验。(5) Vestan将开发和传播一项教育计划，介绍在SLN活检过程中使用荧光染料的好处。目前，大多数黑色素瘤或乳腺癌患者接受SLN活检，该活检采用非荧光蓝色染料Lymphazurin(R)和tc -99m放射性硫胶体制剂。有零星的Lymphazurin(R)短缺，包括2006-07年16个月的全国完全无药可用，可能降低了全国患者护理的质量。Vestan的方法将消除对Lymphazurin(R)的需求，避免高达2%的Lymphazurin(R)过敏反应的风险，消除Lymphazurin(R)对患者的永久性纹身，并使红绿色盲的外科医生获得更好的SLN检测率。Vestan的技术将为其他术中荧光技术奠定基础，以降低医疗保健成本并改善全世界的手术效果，包括农村和社区医院，这些地方可能无法获得术中使用的短寿命放射性同位素。