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

描述（由申请人提供）：Navidea Biopharmaceuticals（Navidea）正在寻求SBIR FastTrack资助支持，以研究其新产品99 mTc-tilmanocept的临床实用性，安全性和有效性，以在手术中识别前哨淋巴结（SLN），以消除早期宫颈癌，旨在改善患者预后并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治愈他们的疾病。为了成功，这些手术必须切除患者的所有癌症。手术后患者体内残留的肿瘤组织可能导致潜在的危及生命的疾病复发。癌症可能扩散（转移）到原发性肿瘤之外的第一个地方是淋巴流中紧邻肿瘤下游的淋巴结（SLN），这是非常常见的。以前和/或目前，它是/是标准的护理在宫颈癌手术中，以消除e20淋巴结，并检查这些淋巴结的癌症的存在。这种手术策略可能会消除任何淋巴结转移，并提供重要的疾病分期信息，指导术后治疗决策。然而，大规模淋巴结切除术经常导致患者出现水肿，这是一种严重的术后并发症，以及其他疾病。或者，外科医生可以识别SLN。如果SLN没有癌症，那么癌症扩散到淋巴引流途径中更下游的其他淋巴结的可能性非常小。正确识别的无癌前哨淋巴结患者可以免于广泛的淋巴结切除，通常避免严重的术后发病率。在宫颈癌患者中使用SLN标测的一个特别关注的问题是，由于宫颈的解剖位置，淋巴引流是双侧进行的。为了有效，SLN必须在宫颈癌手术中双侧检测，以确保SLN识别的完整性和充分性。目前99 mTc-tilmanocept的竞争者在约25%的病例中无法识别双侧SLN。通过拟议的研究，Navidea正在努力评估99 mTc-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99 mTc-tilmanocept新药申请（NDA），以纳入宫颈癌手术中淋巴映射的适应症，从而使99 mTc-tilmanocept的益处扩展到宫颈癌患者。该研究是一项开放标签的患者内研究，研究99 mTc-tilmanocept和另一种定位剂（Lymphazurin（R））用于检测宫颈癌患者的淋巴结。该研究将确定Lymphazurin和99 mTc-tilmanocept对SLN的识别效果相互比较。此外，SLN病理学（假阴性率的全球金标准）将在药物之间以及在手术期间可能切除的所有淋巴结（非SLN）的病理学之间进行对比。该研究还将关注99 mTc-tilmanocept促进双侧SLN检测的能力。该研究将涉及约40例患者，持续1.5年。

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.