Detection of PitNET Tissue During TSS Using Bevacizumab-800CW (DEPARTURE)

University Medical Center Groningen (UMCG)

Status and phase: Completed; Phase 1

Conditions: Pituitary Macroadenoma; Pituitary Adenoma; Pituitary Tumor

Treatments: Drug: Bevacizumab-IRDye800CW; Device: Molecular Fluorescence Endoscopy platform

Study type: Interventional

Funder types: Other

Identifiers

NCT04212793

UMCG 201800170

Details and patient eligibility

About

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.

Enrollment: 20 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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20 participants in 3 patient groups

NIR endoscopic TSS with 4.5 mg bevacizumab-800CW

Experimental group

Description:

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.

Treatment:

Device: Molecular Fluorescence Endoscopy platform

Drug: Bevacizumab-IRDye800CW

NIR endoscopic TSS with 10 mg bevacizumab-800CW

Experimental group

Description:

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.

Treatment:

Device: Molecular Fluorescence Endoscopy platform

Drug: Bevacizumab-IRDye800CW

NIR endoscopic TSS with 25 mg bevacizumab-800CW

Experimental group

Description:

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.

Treatment:

Device: Molecular Fluorescence Endoscopy platform

Drug: Bevacizumab-IRDye800CW