Panitumumab-IRDye800 in Patients With Pancreatic Cancer Undergoing Surgery

Phase 1

Recruiting

• Conditions: Pancreatic Adenocarcinoma
• Interventions: Procedure: Fluorescence Imaging; Biological: Panitumumab; Drug: Panitumumab-IRDye800

• Registration Number: NCT03384238
• Lead Sponsor: Eben Rosenthal

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2017-12-19
• Study First Submitted QC: 2017-12-23
• Study First Posted: 2017-12-27
• Study Start: 2018-02-07
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-14
• Last Update Posted: 2025-02-17
• Primary Completion: 2026-03
• Study Completion: 2027-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 27

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 1b	Panitumumab	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
Cohort 1a	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. 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
Cohort 1d	Panitumumab	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
Cohort 1c	Fluorescence Imaging	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
Cohort 1a	Fluorescence Imaging	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
Cohort 1c	Panitumumab-IRDye800	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
Cohort 1d	Fluorescence Imaging	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
Cohort 1b	Panitumumab-IRDye800	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
Cohort 1c	Panitumumab	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
Cohort 1b	Fluorescence Imaging	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
Cohort 2- Dose Expansion	Fluorescence Imaging	Cohort 2 will receive the optimal dose of Panitumumab-IRDye800 as determined in Cohort 1
Cohort 2- Dose Expansion	Panitumumab	Cohort 2 will receive the optimal dose of Panitumumab-IRDye800 as determined in Cohort 1
Cohort 1a	Panitumumab-IRDye800	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
Cohort 2- Dose Expansion	Panitumumab-IRDye800	Cohort 2 will receive the optimal dose of Panitumumab-IRDye800 as determined in Cohort 1
Cohort 1d	Panitumumab-IRDye800	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

Primary Outcome Measures

Name	Time	Method
Tumor to background ratio (TBR)	1 day	TBR is defined as fluorescence intensity of tumor tissue compared to that of normal surrounding pancreatic tissue.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Stanford University, School of Medicine; 🇺🇸 Palo Alto, California, United States