Clinical trial NCT02736578: Cetuximab-IRDye 800CW and Intraoperative Imaging in Finding Pancreatic Cancer in Patients Undergoing Surgery
Official title: Intraoperative Pancreatic Cancer Detection Using Multimodality Molecular Imaging
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Pancreatic Adenocarcinoma
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2016-04-13
Enrollment: 8
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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: 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.

Eligibility criteria: INCLUSION CRITERIA

* Clinically suspected or biopsy confirmed diagnosis of pancreatic adenocarcinoma
* Planned standard of care surgery with curative intent for pancreatic adenocarcinoma
* ≥ 19 years of age
* Life expectancy of more than 12 weeks
* EITHER

  * Karnofsky performance status of at least 70%, OR
  * Eastern Cooperative Oncology Group (ECOG)/Zubrod level 1
* Hemoglobin ≥ 9 gm/dL
* Platelet count ≥ 100,000/mm\^3
* Magnesium \> the lower limit of normal (LLN) per institution normal lab values
* Potassium \> LLN
* Calcium \> LLN
* Thyroid-stimulating hormone (TSH) \< 13 micro International units/mL

EXCLUSION CRITERIA

* Received an investigational drug within 30 days prior to first dose of cetuximab IRDye800
* Myocardial infarction (MI); cerebrovascular accident (CVA); uncontrolled congestive heart failure (CHF); or unstable angina within 6 months prior to enrollment
* History of infusion reactions to cetuximab or other monoclonal antibody therapies
* Pregnant or breastfeeding
* Evidence of QT prolongation on pretreatment electrocardiography (ECG) (greater than 440 ms in males or greater than 450 ms in females)
* Lab values that in the opinion of the primary surgeon would prevent surgical resection
* Patients receiving class IA (quinidine, procainamide) or class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents

Primary outcomes:
measure: Peri-operative Cetuximab-IRDye800 Fluorescent Imaging, Both Doses
timeFrame: up to 5 days
Secondary outcomes:
measure: Cetuximab-IRDye800 Labeling Intensity in Tumor and Non-Tumor Tissues (Ex Vivo)
timeFrame: up to 14 days
measure: Effect of Cetuximab-IRDye800 Dose on Fluorescence Intensity
timeFrame: up to 14 days
measure: Sensitivity and Specificity of Ex Vivo Fluorescent Imaging
timeFrame: up to 14 days
measure: Cetuximab-IRDye800 Tumor Detection in Lymph Nodes
timeFrame: up to 14 days
measure: Signal-to-Noise Ratio (SNR) by Ex Vivo Photoacoustic Imaging (PAI)
timeFrame: up to 5 days
measure: Signal-to-Noise Ratio (SNR) by In Vivo Photoacoustic Imaging (PAI)
timeFrame: up to 5 days
measure: Toxicity (≥ Grade 2)
timeFrame: Up to 30 days
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: George Poultsides, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Rosenthal EL, Kulbersh BD, Duncan RD, Zhang W, Magnuson JS, Carroll WR, Zinn K. In vivo detection of head and neck cancer orthotopic xenografts by immunofluorescence. Laryngoscope. 2006 Sep;116(9):1636-41. doi: 10.1097/01.mlg.0000232513.19873.da.
citation: Tummers WS, Miller SE, Teraphongphom NT, Gomez A, Steinberg I, Huland DM, Hong S, Kothapalli SR, Hasan A, Ertsey R, Bonsing BA, Vahrmeijer AL, Swijnenburg RJ, Longacre TA, Fisher GA, Gambhir SS, Poultsides GA, Rosenthal EL. Intraoperative Pancreatic Cancer Detection using Tumor-Specific Multimodality Molecular Imaging. Ann Surg Oncol. 2018 Jul;25(7):1880-1888. doi: 10.1245/s10434-018-6453-2. Epub 2018 Apr 17.
citation: Lwin TM, Hoffman RM, Bouvet M. The future of tumour-specific fluorescence-guided surgery for pancreatic cancer. Lancet Gastroenterol Hepatol. 2020 Aug;5(8):715-717. doi: 10.1016/S2468-1253(20)30123-0. Epub 2020 May 14. No abstract available.