Pancreatic Adenocarcinoma, Pancreatic Cancer
Conditions
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.
Interventions
dose finding: 4.5mg; 10mg; 25mg; 50mg
Sponsors
Leiden University Medical Center
University Medical Center Groningen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
phase I/II safety and dose-finding study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Finding optimal dose of Bevacizumab-800CW for intraoperative imaging of pancreatic cancer measured by calculating Target to Background ratios (TBR) | 3 days after tracer injection | TBR of each dose group assessed by intraoperative imaging as well as ex vivo imaging |
| Tracer accumulation in tumor tissue vs normal pancreatic tissue assessed by intraoperatively and ex vivo measuring of the mean fluorescent intensity | up to 6 months | Mean Fluorescent Intensity (MFI) measured in tumor tissue compared to normal pancreatic tissue at macroscopic and microscopic level |
Secondary
| Measure | Time frame |
|---|---|
| Number of participants with treatment-related adverse events | Up to 4 weeks after tracer injection |
Countries
Netherlands
Outcome results
None listed