Detection of PitNET Tissue During TSS Using Bevacizumab-800CW

NCT04212793 | Completed Phase 1

• 1 other identifier: UMCG 201800170
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Pituitary Tumor; Pituitary Adenoma; Pituitary Macroadenoma

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (3)

• The correlation of in vivo and ex vivo fluorescent signals to histopathological analysis results

  Up to 1,5 year

• Quantification of the fluorescent signal by MDSFR/SFF spectroscopy

  Up to 1,5 year

• Assessment of the (sub)-cellular distribution of bevacizumab-800CW by ex vivo fluorescence microscopy

  Up to 1,5 year

Study Arms (3)

NIR endoscopic TSS with 4.5 mg bevacizumab-800CW

EXPERIMENTAL

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.

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

NIR endoscopic TSS with 10 mg bevacizumab-800CW

EXPERIMENTAL

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.

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

NIR endoscopic TSS with 25 mg bevacizumab-800CW

EXPERIMENTAL

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.

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

Interventions

Bevacizumab-IRDye800CW DRUG

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

Also known as: Tracer administration

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

Molecular Fluorescence Endoscopy platform DEVICE

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

Also known as: Fluorescence endoscopy

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

Location

Related Publications (2)

• Schmidt I, Vergeer RA, Postma MR, van den Berg G, Sterkenburg AJ, Korsten-Meijer AGW, Feijen RA, Kruijff S, van Beek AP, den Dunnen WFA, Robinson DJ, van Dijk JMC, Nagengast WB, Kuijlen JMA. Fluorescence detection of pituitary neuroendocrine tumour during endoscopic transsphenoidal surgery using bevacizumab-800CW: a non-randomised, non-blinded, single centre feasibility and dose finding trial [DEPARTURE trial]. Eur J Nucl Med Mol Imaging. 2025 Jan;52(2):660-668. doi: 10.1007/s00259-024-06947-9. Epub 2024 Oct 11.

  PMID: 39390132 DERIVED

• 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.

  PMID: 34620658 DERIVED

MeSH Terms

Conditions

Pituitary Neoplasms

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Hypothalamic Neoplasms; Supratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypothalamic Diseases; Pituitary Diseases; Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: The study is a non-randomized, non-blinded, prospective, single center, pilot dose-finding study.

Study Record Dates

• First Submitted: December 17, 2019
• First Posted: December 30, 2019
• Study Start: October 28, 2020
• Primary Completion: October 24, 2022
• Study Completion: October 24, 2022
• Last Updated: April 14, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)