Near-infrared Image Guided Surgery in Pancreatic Adenocarcinoma (PENGUIN)

Intraoperative Detection of Cancer Tissue in Pancreatic Adenocarcinoma Using a VEGF-targeted Optical Fluorescent Imaging Tracer, A Multicentre Feasibility Dose Escalation Study

There is a need for better visualization of resection margins and detection of small tumor deposits during surgery for pancreatic cancer. Optical molecular imaging of pancreatic ductal adenocarcinoma associated biomarkers is a promising technique to accommodate this need. The biomarker Vascular Endothelial Growth Factor (VEGF-A) is overexpressed in pancreatic cancer tissue versus normal tissue and has proven to be a valid target for molecular imaging. VEGF-A can be targeted by the monoclonal antibody bevacizumab. Monoclonal antibodies can be labeled by the near-infrared (NIR) fluorescent dye IRDye800CW (800CW). The investigators hypothesize that bevacizumab-800CW accumulates in VEGF expressing cancer, enabling pancreatic cancer visualization using a NIR intraoperative camera system. In this pilot intervention study the investigators will determine the optimal dosage of bevacizumab-800CW (4,5 10, 25 or 50mg) to detect pancreatic cancer tissue intraoperatively.

Study Overview

• Status: Terminated
• Conditions: Pancreatic Cancer; Pancreatic Adenocarcinoma
• Intervention / Treatment: Drug: Bevacizumab-800CW

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • University Medical Center Groningen
  • Leiden, Netherlands
    • Leiden University Medical Center
  • Nijmegen, Netherlands
    • Radboud University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18 years.
• Patients with clinical suspicion of pancreatic head cancer who are scheduled to undergo surgical intervention with curative intent
• World Health Organization (WHO) performance score 0-2.
• Signed written informed consent

Exclusion Criteria:

• Medical or psychiatric conditions that compromise the patient's ability to give informed consent.
• Other invasive malignancy
• Pregnant or lactating women. Documentation of a negative pregnancy test must be available for woman of childbearing potential. Woman of childbearing potential are pre- menopausal women with intact reproductive organs and women less than two years after menopause.
• Prior neo-adjuvant chemo- of radiotherapy
• History of infusion reactions to bevacizumab or other monoclonal antibody therapies.
• Inadequately controlled hypertension with or without current antihypertensive medications
• Within 6 months prior to inclusion: myocardial infarction, Transient Ischemic Attack, Cerebral Vascular Accident, pulmonary embolism, uncontrolled chronic hepatic failure, unstable angina pectoris.
• Anticoagulant therapy with vitamine K antagonists
• Patients receiving Class 1A (quinidine, procainamide) or class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents
• Evidence of QTc (corrected QT interval) prolongation on pretreatment ECG (greater than 44ms in males of greater than 450ms in females)
• Magnesium, potassium and calcium below the lower limit of normal range.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group; Bevacizumab-800CW	Drug: Bevacizumab-800CW; dose finding: 4.5mg; 10mg; 25mg; 50mg; Other Names: Bevacizumab-IRDye800CW

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tracer accumulation in tumor tissue vs normal pancreatic tissue assessed by intraoperatively and ex vivo measuring of the mean fluorescent intensity	Mean Fluorescent Intensity (MFI) measured in tumor tissue compared to normal pancreatic tissue at macroscopic and microscopic level	up to 6 months
Finding optimal dose of Bevacizumab-800CW for intraoperative imaging of pancreatic cancer measured by calculating Target to Background ratios (TBR)	TBR of each dose group assessed by intraoperative imaging as well as ex vivo imaging	3 days after tracer injection

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of participants with treatment-related adverse events	Up to 4 weeks after tracer injection

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Collaborators: Leiden University Medical Center
• Investigators: Principal Investigator: Gooitzen van Dam, MD, UMCG

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): February 26, 2018
• Study Completion (Actual): May 1, 2018

Study Registration Dates

• First Submitted: April 11, 2016
• First Submitted That Met QC Criteria: April 14, 2016
• First Posted (Estimate): April 19, 2016

Study Record Updates

• Last Update Posted (Actual): January 28, 2020
• Last Update Submitted That Met QC Criteria: January 25, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: NL50488.042.15

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED