Fluorescein for Sentinel Lymph Node Detection

描述(由申请人提供)：在这个第二阶段的STTR项目中，Vestan医学成像公司将完成其专有配方的荧光药物和用于前哨淋巴结(SLN)活检的新型医疗设备的开发和临床评估，用于黑色素瘤和乳腺癌的外科治疗。Vestan将与犹他大学亨斯迈癌症研究所(HCI)合作，通过一个子奖项，在接受SLN活检的恶性黑色素瘤或乳腺癌患者中进行两个I/II期临床试验。FDA已经为每一项试验授予了IND豁免地位。这两项研究都得到了大学的审查和批准。犹他州IRB的。人机界面和大学。犹他州服务于7个州的地理区域，包括UT、MT、ID、WY、NV东部、CO西部和AZ北部。地理上广阔的患者服务区，以及针对西班牙裔和附近美洲原住民人口中心的外展计划，使这些医院能够迅速招募临床试验的患者，研究人群反映了这一大片地理区域的种族多样性。完成这一新的SLN活检方法的开发和评价的具体目的是：(1)荧光制剂的稳定性测试和通过药代动力学研究确定药物清除率。(2)生产足够数量的原型照明和可视化设备，以供2项临床试验使用。(3)对20名接受黑色素瘤SLN活检术的患者和20名接受SLN活检术的乳腺癌患者进行两项皮下或皮内注射0.001%至1%荧光染料的I期剂量递增研究。(4)对80例接受SLN活检术的恶性黑色素瘤患者和80例接受SLN活检术的乳腺癌患者进行荧光染料和可视化设备的两项统计稳健的II期临床试验。(5)Vestan将开发和传播一项关于在SLN活组织检查过程中使用荧光染料的好处的教育计划。目前，大多数黑色素瘤或乳腺癌患者接受SLN活检术，这种活检术使用了一种非荧光蓝色染料Lymphazurin(R)和一种Tc-99m放射性硫胶制剂。Lymphazurin(R)一直存在零星短缺，包括2006-07年间在全国范围内有16个月完全无法获得，这可能会降低全国患者护理的质量。Vestan的方法将消除对Lymphazurin(R)的需求，避免Lymphazurin(R)高达2%的过敏反应风险，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高的SLN检测率。维斯坦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，改善世界各地的手术结果，包括农村和社区医院，在这些医院，可能不存在获取短期放射性同位素供术中使用的情况。 公共卫生相关性：在接受乳腺癌、恶性黑色素瘤和其他通过淋巴系统转移的癌症患者的手术中，使用荧光药物来定位和直接显示前哨淋巴结(SLN)中的淋巴结在手术室的活检过程中可以取代非荧光和潜在危险的蓝色染料和短暂的放射性同位素。Vestan医学成像公司正在开发的直接荧光可视化技术可能优于目前使用深蓝色染料(Lymphazurin(R))的SLN活组织检查程序，该程序在全国范围内经历了周期性的短缺，包括2006-2007年间16个月的供应不足，以及Tc-99m放射性硫胶体制剂。在全球范围内，从加拿大或英国的反应堆中获得99m的可能性也很小。Vestan的技术旨在降低医疗成本，并改善全球范围内获得最先进医疗保健的机会。Vestan用于SLN活检的荧光技术将使获得短期放射性同位素的农村和社区医院能够为癌症患者提供尽可能好的外科治疗。Vestan已经开发出这项技术，该技术廉价、高效、易于制造，并在完成临床试验后极短的时间内即可投入商业使用。

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.