Fluorescein for Sentinel Lymph Node Detection

用于前哨淋巴结检测的荧光素

• 批准号: 7804829
• 负责人: Robert Hans Ingemar Andtbacka
• 金额: $ 99.94万
• 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/7804829
• 关键词: Agreement; Am 80; Anaphylaxis; Applications Grants; Area; Arts; Back; 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; Fluoresceins; Fluorescence; Fluorescent Dyes; Funding; Geographic Locations; Grant; Health; Health Care Costs; Healthcare; Hispanics; Hospitals; Human; Image; Imagery; Improve Access; Institutes; Internet; 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; Research Ethics Committees; Risk; Rural Community; 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）：在这个第二期 STTR 项目中，Vestan Medical Imaging, Inc. 将完成其荧光药物专利配方和用于前哨淋巴结 (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手术治疗。 Vestan 将通过 Subaward 与犹他大学亨茨曼癌症研究所 (HCI) 合作，对接受恶性黑色素瘤或乳腺癌 SLN 活检的患者进行两项 I/II 期临床试验。 FDA 已授予每项试验 IND 豁免资格。这两项研究均已得到大学的审查和批准。犹他州IRB。 HCI 和大学。犹他州的服务覆盖 7 个州的地理区域，包括犹他州、蒙大拿州、爱达荷州、怀俄明州、内华达州东部、科罗拉多州西部和亚利桑那州北部。地理上较大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快速招募临床试验患者，并拥有反映这一广大地理区域种族多样性的研究人群。完成这种新的前哨淋巴结活检方法的开发和评估的具体目标是：（1）荧光药物制剂的稳定性测试以及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，用于 2 项临床试验。 (3) 对 20 名接受 SLN 活检手术治疗恶性黑色素瘤的患者和 20 名接受 SLN 活检手术治疗乳腺癌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) 对 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 活检的患者进行两项统计稳健的 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好处的教育计划。大多数黑色素瘤或乳腺癌患者目前接受 SLN 活检手术，该手术采用非荧光蓝色染料 Lymphazurin(R) 和 Tc-99m 放射性硫胶体制剂。 Lymphazurin(R) 出现了零星短缺，包括 2006-07 年全国范围内有 16 个月完全无法使用，这可能会降低全国范围内的患者护理质量。 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) 对患者造成的永久性纹身，并允许红绿色盲外科医生获得更好的 SLN 检出率。 Vestan 的技术将为其他术中荧光技术奠定基础，以降低医疗成本并改善全球手术结果，包括可能无法获得术中使用的短寿命放射性同位素的农村和社区医院。 公共健康相关性：在手术室前哨淋巴结 (SLN) 活检过程中，使用荧光药物来定位和直接观察淋巴结，可以取代接受乳腺癌、恶性黑色素瘤和通过淋巴系统转移的其他类型癌症手术的患者使用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优于当前的 SLN 活检程序，该程序使用深蓝色染料 (Lymphazurin(R)) 和 Tc-99m 放射性硫胶体制剂，该染料曾在全国范围内周期性短缺，包括在 2006 年至 2007 年期间有 16 个月无法使用。加拿大或英国的反应堆在全球范围内提供的 Tc-99m 也很脆弱。 Vestan 的技术旨在降低医疗保健成本并提高全球最先进医疗保健的可及性。 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佳的手术护理。 Vestan 开发出的这项技术价格低廉、影响力大、易于制造，并且在临床试验完成后很短的时间内即可商业化。