Intraoperative Detection of Cancer Tissue in Pancreatic Adenocarcinoma Using a VEGF-targeted Optical Fluorescent Imaging Tracer, A Multicentre Feasibility Dose Escalation Study
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Enrollment
- 10
- Locations
- 3
- Primary Endpoint
- Tracer accumulation in tumor tissue vs normal pancreatic tissue assessed by intraoperatively and ex vivo measuring of the mean fluorescent intensity
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Diagnostic
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts 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-
- •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.
Arms & Interventions
Treatment group
Bevacizumab-800CW
Intervention: Bevacizumab-800CW (Drug)
Outcomes
Primary Outcomes
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
Secondary Outcomes
- Number of participants with treatment-related adverse events(Up to 4 weeks after tracer injection)
Investigators
G.M. van Dam
Prof. Dr.
University Medical Center Groningen