Panitumumab-IRDye800 in Patients With Pancreatic Cancer Undergoing Surgery

Study Overview
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Brief Summary
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This phase I/II trial studies the side effects and best dose of panitumumab-IRDye800 and to see how well it works in finding cancer in patients with pancreatic cancer who are undergoing surgery. Panitumumab-IRDye800 is a combination of the antibody drug panitumumab and IRDye800CW, an investigational dye that can be seen using a special camera. Panitumumab-IRDye800 may attach to tumor cells and make them more visible during surgery in patients with pancreatic cancer.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine the optimal dose of panitumumab-IRDye800 in identifying pancreatic cancer compared to surrounding normal tissue in the ex vivo setting as measured by tumor to background ratio. SECONDARY OBJECTIVES: I. Determine the safety and tolerability of the panitumumab-IRDye800 as an imaging agent in subjects undergoing resection of pancreatic cancer. II. Determine whether metastatic lesions, positive lymph node, or residual disease can be detected by near-infrared (NIR) fluorescence imaging with panitumumab-IRDye800 but not by white light. OUTLINE: This is a phase I, dose-escalation study of panitumumab-IRDye800 followed by a phase II study. Patients receive a loading dose of panitumumab intravenously (IV) over 60 minutes, and after 15 minutes of observation, patients then receive panitumumab-IRDye800 IV over 60 minutes on day 0. Patients then undergo surgical resection 2-5 days after panitumumab-IRDye800 administration with imaging using the Novadaq SPY/LUNA, Novadaq IR9000 fluorescence imaging system with open field handheld fluorescence imaging camera, and/or pinpoint endoscopic fluorescence imaging camera, and SurgVision Explorer Air multi spectral fluorescence reflectance system. After completion of study treatment, patients are followed up at 15 and 30 days.

Official Title
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A Phase I/II Study Evaluating the Safety and Pharmacokinetics of Panitumumab-IRDye800 as an Optical Imaging Agent to Detect Pancreas Cancer During Surgical Procedures

Conditions
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Pancreatic Adenocarcinoma

Intervention / Treatment
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* Procedure: Fluorescence Imaging
* Biological: Panitumumab
* Drug: Panitumumab-IRDye800


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinically suspected or biopsy-confirmed diagnosis of pancreatic adenocarcinoma Planned standard of care surgery with curative intent for pancreatic adenocarcinoma Life expectancy of more than 12 weeks 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 per institution normal lab values Potassium > the lower limit of normal per institution normal lab values Calcium > the lower limit of normal per institution normal lab values Thyroid-stimulating hormone (TSH) < 13 micro international units/mL Exclusion Criteria: Received an investigational drug within 30 days prior to first dose of panitumumab-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 panitumumab or other monoclonal antibody therapies Pregnant or breastfeeding Evidence of corrected QT (QTc) prolongation on pretreatment electrocardiography (ECG) (greater than 440 ms in males or greater than 460 ms in females) Lab values that in the opinion of the physician would prevent surgical resection Patients receiving class IA (quinidine, procainamide) or class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1a<br>A test/loading dose of 100 mg of unlabeled Panitumumab (fixed dose) will be administered via a 60 minute IV infusion prior to infusion of the Panitumumab IRDye800. Cohort 1a will receive 25 mg of Panitumumab IRDye800 with a 100 mg unlabeled test/loading dose of Panitumumab. The surgical resection will then occur 2 to 5 days after infusion. Intraoperative imaging will be performed using the intraoperative optical imaging devices | Procedure: Fluorescence Imaging<br>* Undergo fluorescence imaging<br>Biological: Panitumumab<br>* Given IV<br>* Other names: Vectibix;Drug: Panitumumab-IRDye800<br>* Given IV<br>* Other names: RDye800-Panitumumab Conjugate;|
| Experimental: Cohort 1b<br>Cohort 1b will receive 50 mg of Panitumumab IRDye800 with a 100 mg unlabeled test/loading dose of Panitumumab. A test/loading dose of 100 mg of unlabeled Panitumumab (fixed dose) will be administered via a 60 minute IV infusion prior to infusion of the Panitumumab IRDye800. The surgical resection will then occur 2 to 5 days after infusion. Intraoperative imaging will be performed using the intraoperative optical imaging devices | Procedure: Fluorescence Imaging<br>* Undergo fluorescence imaging<br>Biological: Panitumumab<br>* Given IV<br>* Other names: Vectibix;Drug: Panitumumab-IRDye800<br>* Given IV<br>* Other names: RDye800-Panitumumab Conjugate;|
| Experimental: Cohort 1c<br>Cohort 1c will receive 75 mg of Panitumumab IRDye800 with a 100 mg unlabeled test/loading dose of Panitumumab.A test/loading dose of 100 mg of unlabeled Panitumumab (fixed dose) will be administered via a 60 minute IV infusion prior to infusion of the Panitumumab IRDye800. The surgical resection will then occur 2 to 5 days after infusion. Intraoperative imaging will be performed using the intraoperative optical imaging devices | Procedure: Fluorescence Imaging<br>* Undergo fluorescence imaging<br>Biological: Panitumumab<br>* Given IV<br>* Other names: Vectibix;Drug: Panitumumab-IRDye800<br>* Given IV<br>* Other names: RDye800-Panitumumab Conjugate;|
| Experimental: Cohort 1d<br>Cohort 1d will receive a 50 mg dose of Panitumumab IRDye800 and no test/loading dose. A test/loading dose of 100 mg of unlabeled Panitumumab (fixed dose) will be administered via a 60 minute IV infusion prior to infusion of the Panitumumab IRDye800. The surgical resection will then occur 2 to 5 days after infusion. Intraoperative imaging will be performed using the intraoperative optical imaging devices | Procedure: Fluorescence Imaging<br>* Undergo fluorescence imaging<br>Biological: Panitumumab<br>* Given IV<br>* Other names: Vectibix;Drug: Panitumumab-IRDye800<br>* Given IV<br>* Other names: RDye800-Panitumumab Conjugate;|
| Experimental: Cohort 2- Dose Expansion<br>Cohort 2 will receive the optimal dose of Panitumumab-IRDye800 as determined in Cohort 1 | Procedure: Fluorescence Imaging<br>* Undergo fluorescence imaging<br>Biological: Panitumumab<br>* Given IV<br>* Other names: Vectibix;Drug: Panitumumab-IRDye800<br>* Given IV<br>* Other names: RDye800-Panitumumab Conjugate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor to background ratio (TBR) | TBR is defined as fluorescence intensity of tumor tissue compared to that of normal surrounding pancreatic tissue. | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Grade 2 or higher AEs determined to be clinically significant and definitely, probably or possibly related to study drug | Safety events will be recorded over the 30 day observation period. | Up to 30 days | 
| Number of positive lymph nodes per participant, not detected by white light | Determine whether positive lymph nodes can be detected by near-infrared (NIR) fluorescence imaging with Panitumumab-IRDye800 but not by white light. | 1 day | 
| Number of positive resection margins per participant, not detected by white light | Determine whether residual disease at resection margins can be detected by near-infrared (NIR) fluorescence imaging with Panitumumab-IRDye800 but not by white light. | 1 day |