Clinical trial

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

Name

UMCG 201800170

Description

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.

Trial arms

Trial start

2020-10-28

Estimated PCD

2022-10-24

Trial end

2022-10-24

Status

Completed

Phase

Early phase I

Treatment

Bevacizumab-IRDye800CW

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

Arms:

NIR endoscopic TSS with 10 mg bevacizumab-800CW, NIR endoscopic TSS with 25 mg bevacizumab-800CW, NIR endoscopic TSS with 4.5 mg bevacizumab-800CW

Other names:

Tracer administration

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

Arms:

NIR endoscopic TSS with 10 mg bevacizumab-800CW, NIR endoscopic TSS with 25 mg bevacizumab-800CW, NIR endoscopic TSS with 4.5 mg bevacizumab-800CW

Other names:

Fluorescence endoscopy

Size

Primary endpoint

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

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

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

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'SEQUENTIAL', 'interventionModelDescription': 'The study is a non-randomized, non-blinded, prospective, single center, pilot dose-finding study.', 'primaryPurpose': 'DIAGNOSTIC', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 20, 'type': 'ACTUAL'}}

Updated at

2023-04-14

1 organization

1 product

3 indications

Organization

University Medical Center Groningen

Product

Bevacizumab-IRDye800CW

Indication

Pituitary Tumor

Indication

Pituitary adenoma

Indication

Pituitary Macroadenoma