The staging of non-small cell lung cancer (NSCLC) requires comprehensive evaluation of lung lymph nodes, either via complete lymphadenectomy during pulmonary resection or via sampling of lymph nodes using mediastinoscopy (preoperatively or intraoperatively). Prospective randomized controlled trial Z0030, reported in 2011, reported no difference between a complete mediastinal lymph node dissection (MLND) and a more limited mediastinal lymph node sampling (MLNS), provided that a minimum of 18 lymph nodes were found and resected. However, finding even 18 lymph nodes in the mediastinum is a daunting task, especially when the latest ACOSOG recommendations include specific lymph nodes from stations 2R, 4R, 7, 8, 9, and 10R in the right chest and stations 4L, 5, 6, 7, 8, 9, and 10L in the left chest. Currently, lymph node sampling of the lung is time-consuming and technically challenging, which in turn increases the risk of complications and missed lymph nodes. The ideal technology for NSCLC staging would provide sensitive and real-time identification of lung lymph nodes via a 5-mm diameter thoracoscope, without the need for ionizing radiation. Curadel has developed such a technology. The FLARE (FLuorescence-Assisted Resection and Exploration) imaging platform uses low levels of safe, invisible, near-infrared (NIR) fluorescent light to highlight one or more targets during surgery. Our two newest innovations include a minimally-invasive FLARE system compatible with video-assisted thoracoscopic surgery (VATS) and a targeted NIR fluorescent contrast agent (CUR-PS327) that highlights every lymph node in the mediastinum for several hours after a single low-dose intravenous injection. Because NIR light penetrates several millimeters through living tissue and blood, this technology enables MLNS for NSCLC to be performed in real-time and with high sensitivity. Our long-term goal is to minimize anesthesia time, minimize complication rate, and maximize lymph node sampling for patients with NSCLC. To accomplish this goal, we have assembled an international team of highly experienced investigators from academia (Leiden University Medical Center in The Netherlands; LUMC) and industry (Curadel, LLC). Each institution has proven core competencies and unique infrastructures that will be combined and leveraged to complete the aims of the grant. Specifically, we will optimize a 5-mm diameter thoracoscope capable of simultaneous color video, 700 nm NIR fluorescence, and 800 nm fluorescence, develop cGMP-compliant synthesis and aseptic fill-finish of pan lymph node agent CUR-PS327 (800 nm peak emission), perform Clinical Trial Application (IND equivalent) enabling toxicology, and perform Phase 1A (normal human volunteers) and Phase 1B (NSCLC patients undergoing MLNS) first-in-human clinical trials of the technology at the LUMC Centre for Drug Research. Completion of the Specific Aims will position this new technology to have a major impact on the care of patients with lung cancer.
Patients with non-small cell lung cancer require extensive sampling of their lung lymph nodes so that the proper treatment can be recommended. Unfortunately, a minimum of 15-18 small lymph nodes must be sampled from specific locations in the left and right chest, which is both time-consuming and difficult. Curadel has developed a new technology that uses low levels of safe, invisible, near-infrared fluorescent light to make all lung lymph nodes light up like a light bulb. This grant application is focused on optimizing the technology and carefully testing it for the first time in humans.
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