Detection of PitNET Tissue During TSS Using Bevacizumab-800CW
- Conditions
- Pituitary AdenomaPituitary MacroadenomaPituitary Tumor
- Interventions
- Device: Molecular Fluorescence Endoscopy platform
- Registration Number
- NCT04212793
- Lead Sponsor
- University Medical Center Groningen
- Brief Summary
There is a need for improved visualization of presence and extent of pituitary neuroendocrine tumor (PitNET) tissue during transsphenoidal surgery (TSS), especially in tumors invading the cavernous sinus (CS). Optical molecular imaging of PitNET associated biomarkers is a promising technique to accommodate this need. Vascular Endothelial Growth Factor (VEGF-A) is overexpressed in PitNET tissue compared to normal pituitary tissue and has proven to be a valid target for molecular imaging. Bevacizumab is an antibody that binds VEGF-A. By conjugating a fluorescent dye to this antibody, the fluorescent tracer molecule bevacizumab-800CW is created, which binds to VEGF-A. The investigators hypothesize that bevacizumab-800CW accumulates in PitNET tissue, enabling visualization using a molecular fluorescence endoscopy system. In this pilot intervention study the investigators will determine the feasibility of using microdoses (4.5, 10 and 25 mg) of bevacizumab-800CW to detect PitNET tissue intraoperatively.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 20
- Patients with an established diagnosis of PitNET with a Knosp grade of 3 or 4 who are scheduled to undergo TSS.
- WHO performance status 0-2
- Signed written informed consent
- Medical or psychiatric conditions that compromise the patient's ability to give informed consent
- 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
- History of infusion reactions to bevacizumab or other monoclonal antibody therapies.
- Inadequately controlled hypertension with or without current antihypertensive medication
- Within 6 months prior to inclusion: myocardial infarction, TIA, CVA, pulmonary embolism, uncontrolled chronic hepatic failure, unstable angina pectoris
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description NIR endoscopic TSS with 25 mg bevacizumab-800CW Molecular Fluorescence Endoscopy platform IV-administration of 25 mg of the fluorescent tracer bevacizumab-800CW to 3 patients with a pituitary neuroendocrine tumor (PitNET) with a Knosp grade of 3 or 4. The optimal dose will be expanded to include 6 patients. NIR endoscopic TSS with 4.5 mg bevacizumab-800CW Molecular Fluorescence Endoscopy platform IV-administration of 4.5 mg of the fluorescent tracer bevacizumab-800CW to 3 patients with a pituitary neuroendocrine tumor (PitNET) with a Knosp grade of 3 or 4. The optimal dose will be expanded to include 6 patients. NIR endoscopic TSS with 10 mg bevacizumab-800CW Molecular Fluorescence Endoscopy platform IV-administration of 10 mg of the fluorescent tracer bevacizumab-800CW to 3 patients with a pituitary neuroendocrine tumor (PitNET) with a Knosp grade of 3 or 4. The optimal dose will be expanded to include 6 patients. NIR endoscopic TSS with 4.5 mg bevacizumab-800CW Bevacizumab-IRDye800CW IV-administration of 4.5 mg of the fluorescent tracer bevacizumab-800CW to 3 patients with a pituitary neuroendocrine tumor (PitNET) with a Knosp grade of 3 or 4. The optimal dose will be expanded to include 6 patients. NIR endoscopic TSS with 10 mg bevacizumab-800CW Bevacizumab-IRDye800CW IV-administration of 10 mg of the fluorescent tracer bevacizumab-800CW to 3 patients with a pituitary neuroendocrine tumor (PitNET) with a Knosp grade of 3 or 4. The optimal dose will be expanded to include 6 patients. NIR endoscopic TSS with 25 mg bevacizumab-800CW Bevacizumab-IRDye800CW IV-administration of 25 mg of the fluorescent tracer bevacizumab-800CW to 3 patients with a pituitary neuroendocrine tumor (PitNET) with a Knosp grade of 3 or 4. The optimal dose will be expanded to include 6 patients.
- Primary Outcome Measures
Name Time Method Number of participants with adverse events (AE), serious adverse events (SAE) and suspected unexpected serious adverse reactions (SUSAR) Up to 7 days after tracer injection Data collection as a measure of safety and tolerability regarding administration of bevacizumab-800CW
Discrimination of tumorous and non-tumorous tissue based on in vivo and ex vivo fluorescence measurements from bevacizumab-800CW gained during fluorescence endoscopic transsphenoidal surgery of pituitary neuroendocrine tumors (PitNETs) Three days after tracer injection To determine the sensitivity of the marker bevacizumab-800CW in discriminating between tumorous and non-tumorous tissue during endoscopic transsphenoidal surgery of pituitary neuroendocrine tumors (PitNETs) defined as the tumor to background ratio and intrinsic fluorescence
- Secondary Outcome Measures
Name Time Method Assessment of the (sub)-cellular distribution of bevacizumab-800CW by ex vivo fluorescence microscopy Up to 1,5 year Imaging of the distribution of bevacizumab-800CW with a fluorescence microscope
The correlation of in vivo and ex vivo fluorescent signals to histopathological analysis results Up to 1,5 year Correlate the H/E images to the fluorescent images made with multiple ex vivo imaging modalities
Quantification of the fluorescent signal by MDSFR/SFF spectroscopy Up to 1,5 year Multi-diameter single-fiber reflectance with single-fiber fluorescence (MDSFR/SFF) spectroscopy can measure the fluorescence signal quantitatively, both in vivo and ex vivo
Trial Locations
- Locations (1)
University Medical Center Groningen
🇳🇱Groningen, Netherlands