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

Eben Rosenthal

Status and phase: Terminated; Phase 2

Conditions: Pancreatic Adenocarcinoma

Treatments: Drug: Cetuximab-IRDye800; Drug: Cetuximab

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02736578

P30CA124435 (U.S. NIH Grant/Contract)

IRB-35789

PANC0024 (Other Identifier)

NCI-2016-00433 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 8 patients

Sex: All

Ages: 19+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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8 participants in 2 patient groups

Cetuximab IRDye800, 50 mg

Experimental group

Description:

On day 0, participants receive a 100 mg cetuximab loading dose by intravenous infusion (IV), followed 1 hour later by cetuximab-IRDye 800CW IV at 50 mg, followed by surgery with intraoperative imaging within 2 to 5 days.

Treatment:

Drug: Cetuximab

Drug: Cetuximab-IRDye800

Cetuximab IRDye800, 100 mg

Experimental group

Description:

On day 0, participants receive a 100 mg cetuximab loading dose by intravenous infusion (IV), followed 1 hour later by cetuximab-IRDye 800CW IV at 100 mg, followed by surgery with intraoperative imaging within 2 to 5 days.

Treatment:

Drug: Cetuximab

Drug: Cetuximab-IRDye800