Clinical trial NCT04212793: Detection of PitNET Tissue During TSS Using Bevacizumab-800CW
Official title: Detection of Pituitary Neuroendocrine Tumor (PitNET) Tissue During Endoscopic Transsphenoidal Surgery Using Bevacizumab-800CW
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pituitary Tumor
Pituitary Adenoma
Pituitary Macroadenoma
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2019-12-30
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: The study is a non-randomized, non-blinded, prospective, single center, pilot dose-finding study.
Primary purpose: DIAGNOSTIC

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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)
timeFrame: Three days after tracer injection
measure: Number of participants with adverse events (AE), serious adverse events (SAE) and suspected unexpected serious adverse reactions (SUSAR)
timeFrame: Up to 7 days after tracer injection
Secondary outcomes:
measure: The correlation of in vivo and ex vivo fluorescent signals to histopathological analysis results
timeFrame: Up to 1,5 year
measure: Quantification of the fluorescent signal by MDSFR/SFF spectroscopy
timeFrame: Up to 1,5 year
measure: Assessment of the (sub)-cellular distribution of bevacizumab-800CW by ex vivo fluorescence microscopy
timeFrame: Up to 1,5 year
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
References:
citation: Vergeer RA, Postma MR, Schmidt I, Korsten-Meijer AG, Feijen RA, Kruijff S, Nagengast WB, van Dijk JMC, den Dunnen WFA, van Beek AP, Kuijlen JMA, van den Berg G. Detection by fluorescence of pituitary neuroendocrine tumour (PitNET) tissue during endoscopic transsphenoidal surgery using bevacizumab-800CW (DEPARTURE trial): study protocol for a non-randomised, non-blinded, single centre, feasibility and dose-finding trial. BMJ Open. 2021 Oct 7;11(10):e049109. doi: 10.1136/bmjopen-2021-049109.