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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04212793
Recruitment Status : Not yet recruiting
First Posted : December 30, 2019
Last Update Posted : December 30, 2019
Sponsor:
Information provided by (Responsible Party):
Dr. G. van den Berg, University Medical Center Groningen

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.

Condition or disease Intervention/treatment Phase
Pituitary Tumor Pituitary Adenoma Pituitary Macroadenoma Drug: Bevacizumab-IRDye800CW Device: Molecular Fluorescence Endoscopy platform Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: The study is a non-randomized, non-blinded, prospective, single center, pilot dose-finding study.
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Detection of Pituitary Neuroendocrine Tumor (PitNET) Tissue During Endoscopic Transsphenoidal Surgery Using Bevacizumab-800CW
Estimated Study Start Date : March 2020
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : March 2021


Arm Intervention/treatment
Experimental: 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.
Drug: Bevacizumab-IRDye800CW
Intravenous administration of 4.5, 10 or 25 mg of Bevacizumab-IRDye800CW prior to endoscopic transsphenoidal surgery
Other Name: Tracer administration

Device: 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
Other Name: Fluorescence endoscopy

Experimental: 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.
Drug: Bevacizumab-IRDye800CW
Intravenous administration of 4.5, 10 or 25 mg of Bevacizumab-IRDye800CW prior to endoscopic transsphenoidal surgery
Other Name: Tracer administration

Device: 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
Other Name: Fluorescence endoscopy

Experimental: 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.
Drug: Bevacizumab-IRDye800CW
Intravenous administration of 4.5, 10 or 25 mg of Bevacizumab-IRDye800CW prior to endoscopic transsphenoidal surgery
Other Name: Tracer administration

Device: 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
Other Name: Fluorescence endoscopy




Primary Outcome Measures :
  1. 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) [ Time Frame: Three days after tracer injection ]
    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

  2. Number of participants with adverse events (AE), serious adverse events (SAE) and suspected unexpected serious adverse reactions (SUSAR) [ Time Frame: Up to 7 days after tracer injection ]
    Data collection as a measure of safety and tolerability regarding administration of bevacizumab-800CW


Secondary Outcome Measures :
  1. The correlation of in vivo and ex vivo fluorescent signals to histopathological analysis results [ Time Frame: Up to 1,5 year ]
    Correlate the H/E images to the fluorescent images made with multiple ex vivo imaging modalities

  2. Quantification of the fluorescent signal by MDSFR/SFF spectroscopy [ Time Frame: Up to 1,5 year ]
    Multi-diameter single-fiber reflectance with single-fiber fluorescence (MDSFR/SFF) spectroscopy can measure the fluorescence signal quantitatively, both in vivo and ex vivo

  3. Assessment of the (sub)-cellular distribution of bevacizumab-800CW by ex vivo fluorescence microscopy [ Time Frame: Up to 1,5 year ]
    Imaging of the distribution of bevacizumab-800CW with a fluorescence microscope



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04212793


Contacts
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Contact: Gerrit van den Berg, PhD +31503613430 g.van.den.berg@umcg.nl
Contact: Mark R Postma, MD +31503618675 m.r.postma01@umcg.nl

Locations
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Netherlands
University Medical Center Groningen
Groningen, Netherlands, 9713 GZ
Contact: Gerrit van den Berg, PhD    +31503613430    g.van.den.berg@umcg.nl   
Contact: Mark R Postma, MD    +31503618675    m.r.postma01@umcg.nl   
Sponsors and Collaborators
University Medical Center Groningen

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Responsible Party: Dr. G. van den Berg, Principal Investigator, University Medical Center Groningen
ClinicalTrials.gov Identifier: NCT04212793    
Other Study ID Numbers: UMCG 201800170
First Posted: December 30, 2019    Key Record Dates
Last Update Posted: December 30, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Pituitary Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Central Nervous System Diseases
Endocrine Gland Neoplasms
Neoplasms by Site
Hypothalamic Neoplasms
Supratentorial Neoplasms
Brain Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Adenoma
Pituitary Diseases
Hypothalamic Diseases
Brain Diseases
Nervous System Diseases
Endocrine System Diseases
Bevacizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors