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

Primary Purpose

Pituitary Tumor, Pituitary Adenoma, Pituitary Macroadenoma

Status
Completed
Phase
Phase 1
Locations
Netherlands
Study Type
Interventional
Intervention
Bevacizumab-IRDye800CW
Molecular Fluorescence Endoscopy platform
Sponsored by
University Medical Center Groningen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Pituitary Tumor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • University Medical Center Groningen

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

NIR endoscopic TSS with 4.5 mg bevacizumab-800CW

NIR endoscopic TSS with 10 mg bevacizumab-800CW

NIR endoscopic TSS with 25 mg bevacizumab-800CW

Arm 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.

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.

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.

Outcomes

Primary Outcome Measures

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
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

Secondary Outcome Measures

The correlation of in vivo and ex vivo fluorescent signals to histopathological analysis results
Correlate the H/E images to the fluorescent images made with multiple ex vivo imaging modalities
Quantification of the fluorescent signal by MDSFR/SFF spectroscopy
Multi-diameter single-fiber reflectance with single-fiber fluorescence (MDSFR/SFF) spectroscopy can measure the fluorescence signal quantitatively, both in vivo and ex vivo
Assessment of the (sub)-cellular distribution of bevacizumab-800CW by ex vivo fluorescence microscopy
Imaging of the distribution of bevacizumab-800CW with a fluorescence microscope

Full Information

First Posted
December 17, 2019
Last Updated
April 13, 2023
Sponsor
University Medical Center Groningen
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1. Study Identification

Unique Protocol Identification Number
NCT04212793
Brief Title
Detection of PitNET Tissue During TSS Using Bevacizumab-800CW
Acronym
DEPARTURE
Official Title
Detection of Pituitary Neuroendocrine Tumor (PitNET) Tissue During Endoscopic Transsphenoidal Surgery Using Bevacizumab-800CW
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
October 28, 2020 (Actual)
Primary Completion Date
October 24, 2022 (Actual)
Study Completion Date
October 24, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Medical Center Groningen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pituitary Tumor, Pituitary Adenoma, Pituitary Macroadenoma

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
The study is a non-randomized, non-blinded, prospective, single center, pilot dose-finding study.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
NIR endoscopic TSS with 4.5 mg bevacizumab-800CW
Arm Type
Experimental
Arm 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.
Arm Title
NIR endoscopic TSS with 10 mg bevacizumab-800CW
Arm Type
Experimental
Arm 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.
Arm Title
NIR endoscopic TSS with 25 mg bevacizumab-800CW
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab-IRDye800CW
Other Intervention Name(s)
Tracer administration
Intervention Description
Intravenous administration of 4.5, 10 or 25 mg of Bevacizumab-IRDye800CW prior to endoscopic transsphenoidal surgery
Intervention Type
Device
Intervention Name(s)
Molecular Fluorescence Endoscopy platform
Other Intervention Name(s)
Fluorescence endoscopy
Intervention Description
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
Primary Outcome Measure Information:
Title
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)
Description
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
Time Frame
Three days after tracer injection
Title
Number of participants with adverse events (AE), serious adverse events (SAE) and suspected unexpected serious adverse reactions (SUSAR)
Description
Data collection as a measure of safety and tolerability regarding administration of bevacizumab-800CW
Time Frame
Up to 7 days after tracer injection
Secondary Outcome Measure Information:
Title
The correlation of in vivo and ex vivo fluorescent signals to histopathological analysis results
Description
Correlate the H/E images to the fluorescent images made with multiple ex vivo imaging modalities
Time Frame
Up to 1,5 year
Title
Quantification of the fluorescent signal by MDSFR/SFF spectroscopy
Description
Multi-diameter single-fiber reflectance with single-fiber fluorescence (MDSFR/SFF) spectroscopy can measure the fluorescence signal quantitatively, both in vivo and ex vivo
Time Frame
Up to 1,5 year
Title
Assessment of the (sub)-cellular distribution of bevacizumab-800CW by ex vivo fluorescence microscopy
Description
Imaging of the distribution of bevacizumab-800CW with a fluorescence microscope
Time Frame
Up to 1,5 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
University Medical Center Groningen
City
Groningen
ZIP/Postal Code
9713 GZ
Country
Netherlands

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34620658
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.
Results Reference
derived

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Detection of PitNET Tissue During TSS Using Bevacizumab-800CW

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