Fluorescein for Sentinel Lymph Node Detection

用于前哨淋巴结检测的荧光素

• 批准号: 8327612
• 负责人: Robert Hans Ingemar Andtbacka
• 金额: $ 99.55万
• 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 2016-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8327612
• 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）：在本II期STTR项目中，Vestan Medical Imaging，Inc.该公司将完成其荧光药物专利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的前哨淋巴结（SLN）活检的新医疗设备。Vestan将通过Subaward与犹他州大学亨斯迈癌症研究所（HCI）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。FDA已经批准了每项试验的IND豁免。两项研究均已由犹他州大学IRB审查和批准。HCI和犹他州大学服务于7个州的地理区域，包括UT，MT，ID，WY，东部NV，西部CO和北方AZ。地理上庞大的患者服务区和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增加临床试验患者，并具有反映这一大型地理区域种族多样性的研究人群。完成SLN活检新方法的开发和评价的具体目的是：（1）荧光药物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器械，用于2项临床试验。(3)在20例接受SLN活检术治疗恶性黑色素瘤的患者和20例接受SLN活检术治疗乳腺癌的患者中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)在80名接受恶性黑色素瘤SLN活检的患者和80名接受乳腺癌SLN活检的患者中进行两项关于荧光染料和可视化器械的临床稳健的II期临床试验。(5)Vestan将制定并传播一项关于在SLN活检程序中使用荧光染料的益处的教育计划。大多数患有黑色素瘤或乳腺癌的患者目前接受SLN活检程序，该程序采用非荧光蓝色染料Lymphazurin（R）和Tc-99 m放射性硫胶体制剂。在2006- 2007年的16个月里，Lymphazurin（R）出现了零星的短缺，包括在全国范围内完全无法使用，这可能会降低全国范围内的病人护理质量。Vestan的方法将消除对Lymphazurin（R）的需求，避免Lymphazurin（R）引起过敏反应的高达2%的风险，消除Lymphazurin（R）对患者的永久性纹身，并允许患有红-绿色色盲的外科医生实现更好的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球手术结果，包括农村和社区医院，这些医院可能无法获得用于术中使用的短寿命放射性同位素。 公共卫生相关性：在手术室的前哨淋巴结（SLN）活检程序中使用荧光药物定位和直接可视化淋巴结，可以取代接受乳腺癌、恶性黑色素瘤和其他类型通过淋巴系统转移的癌症手术的患者的非荧光和潜在危险的蓝色染料和短寿命放射性同位素。 Vestan Medical Imaging，Inc.正在开发的直接荧光可视化技术。可能上级目前使用深蓝色染料（Lymphazurin（R））的SLN活检程序，该染料经历了周期性的全国性短缺，包括其在2006-2007年的16个月不可用，以及Tc-99 m放射性硫胶体制剂。加拿大或英国的反应堆生产的Tc-99 m在全球范围内的可用性也很脆弱。 Vestan的技术旨在降低医疗保健成本，并改善全球最先进的医疗保健服务。Vestan用于SLN活检的荧光技术将使那些无法获得短寿命放射性同位素的农村和社区医院能够为癌症患者提供最好的手术护理。 Vestan开发的这项技术价格低廉，影响力大，易于制造，并且在完成临床试验后很短的时间内就可以商业化。