99mTc-Tilmanocept for Sentinel Lymph Node Biopsy in Cervical Cancer Surgeries

99mTc-Tilmanocept 在宫颈癌手术中用于前哨淋巴结活检

• 批准号: 8775028
• 负责人: Frederick Oliver Cope
• 金额: $ 16.59万
• 依托单位: NAVIDEA BIOPHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-30 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8775028
• 关键词: Adverse event; Amendment; Avidity; Beds; Binding; Biological; Biological Products; Breast; Breast Melanoma; Cancer Patient; Cell surface; Cervix Neoplasms; Cervix Uteri; Clinical; Clinical Research; Comparative Study; Contracts; Cutaneous; Data Analyses; Dendritic Cells; Detection; Diagnostic; Disease; Dissection; Drainage procedure; Dyes; Evaluation; Excision; FDA approved; Gap Junctions; Goals; Gold; Grant; Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma; Head and neck structure; Institutional Review Boards; Label; Lead; Letters; Life; Lymph Node Dissections; Lymphatic; Lymphazurin; Lymphedema; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Maps; Marketing; Morbidity - disease rate; Neoplasm Metastasis; Nodal; Operative Surgical Procedures; Oral; Outcome; Pathology; Pathway interactions; Patients; Performance; Pharmaceutical Preparations; Phase II Clinical Trials; Phase III Clinical Trials; Positioning Attribute; Primary Neoplasm; Procedures; Qualifying; Quality of Care; Radioactive; Radiolabeled; Radiopharmaceuticals; Recurrence; Recurrent disease; Residual Tumors; Resources; Risk; Safety; Secure; Sentinel Lymph Node; Sentinel Lymph Node Biopsy; Sentinel Lymph Node Mapping; Serious Adverse Event; Small Business Innovation Research Grant; Solid Neoplasm; Specificity; Staging; Stream; Surgeon; Surgical complication; Therapeutic; Tumor Tissue; cancer surgery; cancer type; clinically significant; design; disorder risk; improved; lymph nodes; macrophage; malignant breast neoplasm; mannose receptor; melanoma; open label; operation; performance site; public health relevance; radiotracer; standard of care; theories; tumor

DESCRIPTION (provided by applicant): Navidea Biopharmaceuticals (Navidea) is seeking SBIR FastTrack grant support to investigate the clinical utility, safety, and efficacy of its new product, 99mTc-tilmanocept, to identify sentinel lymph nodes (SLNs) during surgeries to remove early stage cervical cancers with the intent of improving patient outcomes and reducing post-surgical morbidities in patients undergoing these operations. Cancer patients can frequently be cured of their illnesses by surgeries that remove their tumors. To be successful, these surgeries must remove all of a patient's cancer. Residual tumor tissue in patients after surgery can result in potentially life threatening disease recurrences. It is very common that the first places to which a cancer may spread (metastasize) beyond the primary tumor are to lymph nodes that are immediately downstream from the tumor in the lymphatic flow, the SLNs. Previously and/or currently, it is/was standard of care in cervical cancer surgeries to remove e20 lymph nodes and examine these lymph nodes for the presence of cancer. This surgical strategy presumably removes any lymph node metastases and provides important disease staging information that guides postsurgical treatment decisions. However, wholesale lymph node removal frequently causes patients to develop lymphedema, a serious post-surgical complication, among other morbidities. Alternatively, a surgeon can identify the SLNs. If the SLNs are free of cancer, it is very unlikely that cancer has spread to other lymph nodes further downstream in the lymphatic drainage pathways. Patients with cancer free correctly identified SLNs can be spared from extensive node removal, frequently avoiding serious post-surgical morbidities. A particular concern in using SLN mapping in cervical cancer patients is that because of the anatomical position of the cervix, lymphatic drainage proceeds bilaterally. In order to be effective, SLNs must be detected bilaterally in cervical cancer surgeries for SLN identification to be considered complete and adequate. Current competitors of 99mTc-tilmanocept cannot identify SLNs bilaterally in ~25% of cases. With the proposed study, Navidea is initiating efforts to evaluate 99mTc-tilmanocept's SLN identification performance in cervical cancer surgeries. Ultimately, the goal of this project is to amend the 99mTc-tilmanocept New Drug Application (NDA) to include an indication for lymphatic mapping in cervical cancer surgeries, thus permitting the benefits of 99mTc-tilmanocept to be extended to cervical cancer patients. The proposed study is designed as an open-label, within-patient study of 99mTc-tilmanocept and an alternative mapping agent (Lymphazurin(R)) for detection of nodes in patients with cervical cancer. The study will determine how well SLN identification with Lymphazurin and 99mTc-tilmanocept compare with each other. Additionally, the SLN pathology, the global gold standard for false negative rates, will be contrasted between agents and between the pathology of all nodes that may be removed during the procedure (non-SLNs). The study will also focus on the ability of 99mTc-tilmanocept to facilitate detection of SLNs bilaterally. The study will involve ~40 patients and last 1.5 yrs.

描述(由申请人提供)：Navidea BiopPharmticals(Navidea)正在寻求SBIR FastTrack赠款支持，以调查其新产品99mTc-tilmanocept的临床实用性、安全性和有效性，以在切除早期宫颈癌的手术中识别前哨淋巴结(SLN)，目的是改善患者预后，降低接受这些手术的患者的术后发病率。癌症患者通常可以通过切除肿瘤的手术来治愈疾病。为了取得成功，这些手术必须切除患者的所有癌症。患者手术后残留的肿瘤组织可能会导致潜在的危及生命的疾病复发。非常常见的是，癌症可能首先扩散到(转移)原发肿瘤以外的地方是淋巴流动中紧邻肿瘤下游的淋巴结，即SLN。以前和/或现在，宫颈癌手术的标准护理是切除E20淋巴结并检查这些淋巴结是否存在癌症。这一手术策略可能会移除任何淋巴转移，并提供重要的疾病分期信息，指导手术后的治疗决定。然而，大规模的淋巴结切除经常会导致患者发生淋巴水肿，这是一种严重的术后并发症，以及其他并发症。或者，外科医生可以识别SLN。如果SLN没有癌症，癌症就不太可能扩散到淋巴引流路径下游的其他淋巴结。诊断正确的无癌SLN患者可以避免广泛的结节切除，经常避免严重的手术后并发症。在宫颈癌患者中使用SLN标测时特别需要注意的是，由于宫颈的解剖位置，淋巴引流是双侧进行的。为了有效，必须在宫颈癌手术中双侧检测SLN，以使SLN识别被认为是完整和充分的。目前99mTc-tilmanocept的竞争对手在约25%的病例中无法双侧识别SLN。通过这项拟议的研究，Navidea正在着手评估99mTC-tilmanocept在宫颈癌手术中的SLN识别性能。最终，该项目的目标是修改99mTc-tilmanocept新药申请(NDA)，以包括宫颈癌手术中淋巴映射的适应症，从而允许99mTc-tilmanocept的益处扩展到宫颈癌患者。这项拟议的研究被设计为99mTC-tilmanocept和一种替代标记剂(Lymphazurin(R))的开放标签患者内研究，用于检测宫颈癌患者的结节。这项研究将确定Lymphazurin和99mTc-tilmanocept对SLN的识别效果如何。此外，作为假阴性率的全球黄金标准，SLN病理将在不同的试剂之间以及在手术过程中可能被切除的所有结节(非SLN)的病理之间进行对比。这项研究还将侧重于99mTC-替马诺普促进双侧SLN检测的能力。这项研究将涉及约40名患者，持续时间为1.5年。