Cetuximab-IRDye 800CW and Intraoperative Imaging in Finding Pancreatic Cancer in Patients Undergoing Surgery

Brief summary public domain (ClinicalTrials.gov)

This phase 1-2 trial studies the side effects and best dose of cetuximab-IRDye 800CW when used with intraoperative imaging, to determine the utility of cetuximab-IRDye 800CW to identify and assess pancreatic cancer in patients undergoing surgery to remove the tumor. Cetuximab-IRDye 800CW may help doctors better identify cancer in the operating room by making the cancer visible when viewed through a fluorescent imaging system.

Detailed description public domain (ClinicalTrials.gov)

This is a dose-escalation study of 50 mg or 100 mg cetuximab-IRDye800. Clearance of the tumor margin during surgical resection of pancreatic cancer is clinical importance, as margin-positive resections are suspected to be associated with rapid emergence of distant metastases shortly after surgery. However, pancreatic cancer is known to be difficult to visualize intraoperatively. Nonetheless, better detection of tumor tissue might improve the rate of complete tumor clearance, thereby improving outcomes. However, in order to be actionable, the data from such enhanced tumor detection must be available during the resection procedure. This study evaluates the use of a dye, Cetuximab-IRDye 800CW, that is administered pre-surgery, and is detectable during the surgical procedure. Florescent Imaging Cetuximab is a chimeric (mouse/human) monoclonal antibody that targets the epidermal growth factor (EGF) receptor (EGFR). EGFR is highly-expressed in pancreatic ductal adenocarcinoma (PDAC) and is a good target for antibody-mediated imaging, due to its transmembrane position. Cetuximab-IRDye 800CW is cetuximab labeled with IRDye800, an N-hydroxysuccinimide (NHS) ester infrared dye. IRDye800 has very similar properties compared to indocyanine green, and indocyanine green is readily detectable with a number of imaging systems. This study evaluates the Cetuximab-IRDye 800CW as a intraoperative labeling agent. Patients receive Cetuximab-IRDye 800CW intravenously (IV) at 50 mg or 100 mg over 30 minutes to 1 hour on day 0. Within 2 to 5 days, patients undergo surgery with intraoperative imaging. Cetuximab-IRDye 800CW is used as part of a tumor-targeted molecular imaging procedure operating on the principles of differential accumulation of the antibody-dye conjugate in pancreatic tumor tissue vs normal pancreatic tissue vs pancreatitis tissue. Excised tissues are prepared as formalin-fixed paraffin-embedded (FFPE) blocks for assessment of fluorescent intensity. Photoacoustic imaging (PAI) For purposes of non-quantitative comparison, photoacoustic imaging (PAI) of the tumor lesions is also conducted. PAI refers to a non-invasive evaluation by ultrasound of the area of the resected tumor and surrounding tissue. PAI may have special utility for detecting tumors within 5 to 7 mm of depth, with a high degree of spatial resolution, which might be useful to enhance generation of tumor-free surgical margins. PAI does not utilize ionizing radiation, and should complement and conform to the findings from the fluorescent imaging. PRIMARY OBJECTIVE: Determine the efficacy of cetuximab-IRDye800 in intraoperatively identifying pancreatic cancer compared to surrounding normal pancreatic and extrapancreatic tissue, as measured by tumor-to-background ratio. SECONDARY OBJECTIVE: Determine the tolerability of the cetuximab IRDye800 as an imaging agent in patients undergoing resection of pancreatic cancer.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Peri-operative Cetuximab-IRDye800 Fluorescent Imaging, Both Doses [up to 5 days]. Mean, ratio (Standard Deviation). In vivo (tumor at resection): Cetuximab IRDye800, 50 mg (n=6): 2.3 (0.72). In vivo (lymph node at resection): Cetuximab IRDye800, 50 mg (n=6): 6.3 (0.82). Ex vivo (post-operative, back-table): Cetuximab IRDye800, 50 mg (n=6): 3.4 (0.4).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Cetuximab-IRDye800 Labeling Intensity in Tumor and Non-Tumor Tissues (Ex Vivo) [up to 14 days]. Mean, counts per pixel (Standard Deviation). Normal pancreatic tissue: Cetuximab IRDye800, 50 mg (n=6): 0.02 (0.01). Pancreatitis tissue: Cetuximab IRDye800, 50 mg (n=6): 0.04 (0.02). Pancreatic tumor tissue: Cetuximab IRDye800, 50 mg (n=6): 0.09 (0.06).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Effect of Cetuximab-IRDye800 Dose on Fluorescence Intensity [up to 14 days]. Mean, counts per pixel (Standard Deviation). Normal pancreatic tissue: Cetuximab IRDye800, 50 mg (n=4): 0.02 (0.01); Cetuximab IRDye800, 100 mg (n=2): 0.03 (0.02). Pancreatitis tissue: Cetuximab IRDye800, 50 mg (n=4): 0.03 (0.02); Cetuximab IRDye800, 100 mg (n=2): 0.06 (0.03). Pancreatic tumor tissue: Cetuximab IRDye800, 50 mg (n=4): 0.09 (0.06); Cetuximab IRDye800, 100 mg (n=2): 0.10 (0.05).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Sensitivity and Specificity of Ex Vivo Fluorescent Imaging [up to 14 days]. Number, percentage of lymph nodes. Sensitivity: Cetuximab IRDye800, 50 mg (n=4): 100.0; Cetuximab IRDye800, 100 mg (n=2): 88.2; Cetuximab IRDye800, Both Doses (n=6): 96.1. Specificity: Cetuximab IRDye800, 50 mg (n=4): 78.0; Cetuximab IRDye800, 100 mg (n=2): 32.1; Cetuximab IRDye800, Both Doses (n=6): 67.0.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Cetuximab-IRDye800 Tumor Detection in Lymph Nodes [up to 14 days]. Mean, counts per pixel (Standard Error). Tumor-bearing lymph nodes: Cetuximab IRDye800, 50 mg (n=4): 0.071 (0.01); Cetuximab IRDye800, 100 mg (n=2): 0.046 (0.007). Histologically normal lymph nodes: Cetuximab IRDye800, 50 mg (n=4): 0.018 (0.001); Cetuximab IRDye800, 100 mg (n=2): 0.035 (0.004).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Signal-to-Noise Ratio (SNR) by Ex Vivo Photoacoustic Imaging (PAI) [up to 5 days]. Number, ratio. Cetuximab IRDye800, 50 mg (n=4): 3.7.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Signal-to-Noise Ratio (SNR) by In Vivo Photoacoustic Imaging (PAI) [up to 5 days].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Toxicity (≥ Grade 2) [Up to 30 days]. Number, Adverse events. Cetuximab IRDye800, 50 mg (n=6): 1; Cetuximab IRDye800, 100 mg (n=2): 0.