Cetuximab-IRDye 800CW and Intraoperative Imaging in Finding Pancreatic Cancer in Patients Undergoing Surgery
| Status: | Terminated |
|---|---|
| Conditions: | Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 19 - Any |
| Updated: | 2/3/2019 |
| Start Date: | July 2016 |
| End Date: | May 22, 2017 |
Intraoperative Pancreatic Cancer Detection Using Multimodality Molecular Imaging
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.
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.
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.
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.
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
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