Detection of Pituitary Neuroendocrine Tumor (PitNET) Tissue During Endoscopic Transsphenoidal Surgery Using Bevacizumab-800CW
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Number of participants with adverse events (AE), serious adverse events (SAE) and suspected unexpected serious adverse reactions (SUSAR)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Bevacizumab-IRDye800CW (Drug)
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.
干预措施: Molecular Fluorescence Endoscopy platform (Device)
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.
干预措施: Bevacizumab-IRDye800CW (Drug)
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.
干预措施: Molecular Fluorescence Endoscopy platform (Device)
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.
干预措施: Bevacizumab-IRDye800CW (Drug)
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.
干预措施: Molecular Fluorescence Endoscopy platform (Device)
结局指标
主要结局
Number of participants with adverse events (AE), serious adverse events (SAE) and suspected unexpected serious adverse reactions (SUSAR)
时间窗: Up to 7 days after tracer injection
Data collection as a measure of safety and tolerability regarding administration of bevacizumab-800CW
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)
时间窗: 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
次要结局
- 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)
研究者
Jos M. A. Kuijlen
Principal Investigator
University Medical Center Groningen