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

• ClinicalTrials.gov Identifier: NCT02743975
• Recruitment Status: Terminated
• First Posted: April 19, 2016
• Last Update Posted: January 28, 2020
• Sponsor: University Medical Center Groningen
• Collaborator: Leiden University Medical Center
• Information provided by (Responsible Party): G.M. van Dam, University Medical Center Groningen

Tracking Information

• First Submitted Date: April 11, 2016
• First Posted Date: April 19, 2016
• Last Update Posted Date: January 28, 2020
• Actual Study Start Date: December 1, 2016
• Actual Primary Completion Date: February 26, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 14, 2016)

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

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: April 14, 2016): Number of participants with treatment-related adverse events [ Time Frame: Up to 4 weeks after tracer injection ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Near-infrared Image Guided Surgery in Pancreatic Adenocarcinoma
• Official Title: Intraoperative Detection of Cancer Tissue in Pancreatic Adenocarcinoma Using a VEGF-targeted Optical Fluorescent Imaging Tracer, A Multicentre Feasibility Dose Escalation Study
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

phase I/II safety and dose-finding study

Masking: None (Open Label)
Primary Purpose: Diagnostic

Condition

• Pancreatic Cancer
• Pancreatic Adenocarcinoma

Intervention

Drug: Bevacizumab-800CW

dose finding: 4.5mg; 10mg; 25mg; 50mg

Other Name: Bevacizumab-IRDye800CW

Study Arms

Experimental: Treatment group

Bevacizumab-800CW

Intervention: Drug: Bevacizumab-800CW

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: January 25, 2020): 10
• Original Estimated Enrollment (submitted: April 14, 2016): 26
• Actual Study Completion Date: May 1, 2018
• Actual Primary Completion Date: February 26, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT02743975
• Other Study ID Numbers: NL50488.042.15
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: G.M. van Dam, University Medical Center Groningen
• Study Sponsor: University Medical Center Groningen
• Collaborators: Leiden University Medical Center

Investigators

• Principal Investigator: Gooitzen van Dam, MD; UMCG

• PRS Account: University Medical Center Groningen
• Verification Date: January 2020