Evidence from our lab and others has demonstrated the potential of fluorescently labeled antibodies to measure microscopic disease to guide surgical intervention preclinical models. We present novel data demonstrating safety of the fluorescently labeled anti-EGFR antibody in non- human primates and humans. We propose a clinical trial in collaboration with Novadaq to develop a prototype intraoperative imaging device for use in a first in human clinical trial with fluorescently labeled panitumumab. The trial will b designed to test safety of the drug and determine if the camera can detect subclinical cancer in the operating room to guide surgical resection of head and neck cancer. The cGMP manufacture of panitumumab-dye is being completed by the NCI NExT program.
Because of the crude techniques surgeons currently use to assess tumors, it is not surprising that tumor margins are positive in 30% of head and neck cancer (HNC) resections. If tumor margins could be accurately assessed intraoperatively, it is possible that less healthy tissue would be removed and survival rates improved. We have previously demonstrated intravenous administration of fluorescently labeled anti-EGFR antibody can image microscopic tumor fragments in multiple preclinical models. Furthermore, we present novel data demonstrating the safety of anti-EGFR-IRDye800 in non-human primate and human studies. We propose to develop a prototype device designed for intraoperative cancer detection developed by Novadaq for use in a clinical trial using a novel antibody-dye. We propose to assess an FDA approved targeting molecule (panitumumab) to improve safety, limit time to translation, and establish proof of principle for optical imaging guided surgery. We plan to administer escalating doses of panitumumab-IRDye800 to determine safety and tumor specificity in humans and evaluate role of fluorescent histopathological review of resected tumors and regional lymphatics. We conducted a PreIND Meeting on October 15, 2013 which established that no additional toxicology testing was required for IND approval, parameters for manufacture of panitumumab- IRDye800 and direction for the clinical protocol. The NCI/NExT Program is committed to manufacture of panitumumab-IRDye800.
|Gao, Rebecca W; Teraphongphom, Nutte; de Boer, Esther et al. (2018) Safety of panitumumab-IRDye800CW and cetuximab-IRDye800CW for fluorescence-guided surgical navigation in head and neck cancers. Theranostics 8:2488-2495|
|Tummers, Willemieke S; Miller, Sarah E; Teraphongphom, Nutte T et al. (2018) Intraoperative Pancreatic Cancer Detection using Tumor-Specific Multimodality Molecular Imaging. Ann Surg Oncol 25:1880-1888|
|Miller, Sarah E; Tummers, Willemieke S; Teraphongphom, Nutte et al. (2018) First-in-human intraoperative near-infrared fluorescence imaging of glioblastoma using cetuximab-IRDye800. J Neurooncol 139:135-143|
|Gao, Rebecca W; Teraphongphom, Nutte T; van den Berg, Nynke S et al. (2018) Determination of Tumor Margins with Surgical Specimen Mapping Using Near-Infrared Fluorescence. Cancer Res 78:5144-5154|
|Tummers, Willemieke S; Rosenthal, Eben L; Vahrmeijer, Alexander L et al. (2018) ASO Author Reflections: Fluorescent-Guided Surgery to Augment Pancreatic Cancer Surgery. Ann Surg Oncol :|
|Harmsen, Stefan; Teraphongphom, Nutte; Tweedle, Michael F et al. (2017) Optical Surgical Navigation for Precision in Tumor Resections. Mol Imaging Biol 19:357-362|
|Teraphongphom, Nutte; Kong, Christina S; Warram, Jason M et al. (2017) Specimen mapping in head and neck cancer using fluorescence imaging. Laryngoscope Investig Otolaryngol 2:447-452|
|Tummers, Willemieke S; Warram, Jason M; Tipirneni, Kiranya E et al. (2017) Regulatory Aspects of Optical Methods and Exogenous Targets for Cancer Detection. Cancer Res 77:2197-2206|
|Rosenthal, Eben L; Moore, Lindsay S; Tipirneni, Kiranya et al. (2017) Sensitivity and Specificity of Cetuximab-IRDye800CW to Identify Regional Metastatic Disease in Head and Neck Cancer. Clin Cancer Res 23:4744-4752|
|Zhang, Ray R; Schroeder, Alexandra B; Grudzinski, Joseph J et al. (2017) Beyond the margins: real-time detection of cancer using targeted fluorophores. Nat Rev Clin Oncol 14:347-364|
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