Detection of PitNET Tissue During TSS Using Bevacizumab-800CW

NCT ID: NCT04212793

Last Updated: 2023-04-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-28
• Study Completion Date: 2022-10-24

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

NIR endoscopic TSS with 4.5 mg bevacizumab-800CW

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.

Group Type: EXPERIMENTAL

Bevacizumab-IRDye800CW

Intervention Type: DRUG

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

Molecular Fluorescence Endoscopy platform

Intervention Type: 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

NIR endoscopic TSS with 10 mg bevacizumab-800CW

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.

Group Type: EXPERIMENTAL

Bevacizumab-IRDye800CW

Intervention Type: DRUG

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

Molecular Fluorescence Endoscopy platform

Intervention Type: 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

NIR endoscopic TSS with 25 mg bevacizumab-800CW

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.

Group Type: EXPERIMENTAL

Bevacizumab-IRDye800CW

Intervention Type: DRUG

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

Molecular Fluorescence Endoscopy platform

Intervention Type: 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

Interventions

Bevacizumab-IRDye800CW

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

Intervention Type: DRUG

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

Intervention Type: DEVICE

Other Intervention Names

Tracer administration; Fluorescence endoscopy

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Medical Center Groningen

OTHER

Sponsor Role: lead

Responsible Party

Jos M. A. Kuijlen

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University Medical Center Groningen

Groningen, , Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 39390132 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34620658 (View on PubMed)

Other Identifiers

UMCG 201800170

Identifier Type: -

Identifier Source: org_study_id