Detection of PitNET Tissue During TSS Using Bevacizumab-800CW

Pituitary Adenoma Clinical Trial

— DEPARTURE  

Official title:

Detection of Pituitary Neuroendocrine Tumor (PitNET) Tissue During Endoscopic Transsphenoidal Surgery Using Bevacizumab-800CW

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04212793
• Other study ID #: UMCG 201800170
• Status: Completed
• Phase: Phase 1
• Start date: October 28, 2020
• Est. completion date: October 24, 2022

Study information

• Verified date: April 2023
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: October 24, 2022
• Est. primary completion date: October 24, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Adenoma
• Pituitary Adenoma
• Pituitary Diseases
• Pituitary Macroadenoma
• Pituitary Neoplasms
• Pituitary Tumor

Intervention

Drug:
• Bevacizumab-IRDye800CW
Intravenous administration of 4.5, 10 or 25 mg of Bevacizumab-IRDye800CW prior to endoscopic transsphenoidal surgery

Device:
• Molecular Fluorescence Endoscopy platform
A flexible fluorescence fiber-bundle is attached to a fluorescence camera platform to enable the detection of fluorescence signals. The fluorescence fiber-probe is inserted through the standard working channel of the Surgvision explorer endoscope. During surgery, three imaging moments are defined in which the fluorescence molecular endoscopy system will detect the fluorescent signal

Locations

Country	Name	City	State
Netherlands	University Medical Center Groningen	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	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	Three days after tracer injection
Primary	Number of participants with adverse events (AE), serious adverse events (SAE) and suspected unexpected serious adverse reactions (SUSAR)	Data collection as a measure of safety and tolerability regarding administration of bevacizumab-800CW	Up to 7 days after tracer injection
Secondary	The correlation of in vivo and ex vivo fluorescent signals to histopathological analysis results	Correlate the H/E images to the fluorescent images made with multiple ex vivo imaging modalities	Up to 1,5 year
Secondary	Quantification of the fluorescent signal by MDSFR/SFF spectroscopy	Multi-diameter single-fiber reflectance with single-fiber fluorescence (MDSFR/SFF) spectroscopy can measure the fluorescence signal quantitatively, both in vivo and ex vivo	Up to 1,5 year
Secondary	Assessment of the (sub)-cellular distribution of bevacizumab-800CW by ex vivo fluorescence microscopy	Imaging of the distribution of bevacizumab-800CW with a fluorescence microscope	Up to 1,5 year