Fluorescence Molecular Endoscopy of Locally Advanced Esophageal Carcinoma Using Bevacizumab-800CW to Evaluate Dose Response After Neoadjuvant Chemoradiotherapy: a Single-center Feasibility Study.
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Safety of bevacizumab-800CW administration by monitoring vital signs and/or (serious) adverse events.
研究概览
简要总结
For locally advanced esophageal cancer (EC), neoadjuvant chemoradiotherapy (nCRT) for 5 weeks followed by esophagectomy and lymphadenectomy, if necessary, is standard of care. It is reported that the pathological complete response (pCR) rate after nCRT ranges from 16% to 43%, with a median of 26.5%. According to current clinical guidelines, patients who achieved pCR still go for surgery even though those patients who achieved pCR may not benefit from surgery. Besides, about 50% of EC patients may have post-operative complications including pneumonia, anastomotic leakage, recurrent laryngeal nerve paralysis, which lead to low health-related quality of life (HQoL).
The golden standard to test the pathological response is by pathological assessment of the surgical specimen and thus after surgery. Theoretically, if pCR after nCRT can be predicted accurately before surgery by advanced imaging techniques, patients could have a wait-and-see. The wait-and-see procedure includes regular follow-up and salvage surgery if recurrence is present. Therefore, molecular fluorescence endoscopy (FME) using near-infrared fluorescence (NIRF) tracer bevacizumab-800CW targeting vascular endothelial growth factor combined with high-definition white light (HD-WL) endoscopy is expected to be a promising technique to monitor pCR and fill the gap.
详细描述
See brief summary
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •Locally advanced esophageal carcinoma (cT1b-4a N0-3 M0) in multi-disciplinary esophageal oncology meeting agreed on long course neoadjuvant chemoradiotherapy, followed by esophagectomy;
- •Age ≥ 18 years;
- •Written informed consent.
排除标准
- •Patients with psychological diseases or medical issues who are not able to sign informed consent form;
- •Concurrent uncontrolled medical conditions;
- •Pregnancy or breast feeding. A negative pregnancy test must be available for women of childbearing potential (i.e. premenopausal women with intact reproductive organs and women less than two years after menopause);
- •Irradical endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) of primary tumor prior to start of neoadjuvant chemoradiotherapy
- •Received a different investigational drug within 30 days prior to the dose of bevacizumab-800CW;
- •History of infusion reactions to bevacizumab or other monoclonal antibodies;
研究组 & 干预措施
NIR endoscopy with 4.5 mg bevacizumab-800CW
A non-randomized, non-blinded, prospective, feasibility study.
- IV-administration of 4.5 mg of the fluorescent tracer bevacizumab-800CW to a total of 5 patients with locally advanced esophageal cancer. The optimal dose will be expanded to include 30 patients.
- Molecular fluorescence endoscopy: 2-3 days after administration, molecular fluorescence endoscopy will be performed with additional measurements of fluorescence signals.
干预措施: Bevacizumab-IRDye800CW (Drug)
NIR endoscopy with 4.5 mg bevacizumab-800CW
A non-randomized, non-blinded, prospective, feasibility study.
- IV-administration of 4.5 mg of the fluorescent tracer bevacizumab-800CW to a total of 5 patients with locally advanced esophageal cancer. The optimal dose will be expanded to include 30 patients.
- Molecular fluorescence endoscopy: 2-3 days after administration, molecular fluorescence endoscopy will be performed with additional measurements of fluorescence signals.
干预措施: Molecular Fluorescence Endoscopy platform (Device)
NIR endoscopy with 10 mg bevacizumab-800CW
A non-randomized, non-blinded, prospective, feasibility study.
- IV-administration of 10 mg of the fluorescent tracer bevacizumab-800CW to a total of 3 patients with locally advanced esophageal cancer. The optimal dose will be expanded to include 30 patients.
- Molecular fluorescence endoscopy: 2-3 days after administration, molecular fluorescence endoscopy will be performed with additional measurements of fluorescence signals.
干预措施: Bevacizumab-IRDye800CW (Drug)
NIR endoscopy with 10 mg bevacizumab-800CW
A non-randomized, non-blinded, prospective, feasibility study.
- IV-administration of 10 mg of the fluorescent tracer bevacizumab-800CW to a total of 3 patients with locally advanced esophageal cancer. The optimal dose will be expanded to include 30 patients.
- Molecular fluorescence endoscopy: 2-3 days after administration, molecular fluorescence endoscopy will be performed with additional measurements of fluorescence signals.
干预措施: Molecular Fluorescence Endoscopy platform (Device)
NIR endoscopy with 25 mg bevacizumab-800CW
A non-randomized, non-blinded, prospective, feasibility study.
- IV-administration of 25 mg of the fluorescent tracer bevacizumab-800CW to a total of 3 patients with locally advanced esophageal cancer. The optimal dose will be expanded to include 30 patients.
- Molecular fluorescence endoscopy: 2-3 days after administration, molecular fluorescence endoscopy will be performed with additional measurements of fluorescence signals.
干预措施: Bevacizumab-IRDye800CW (Drug)
NIR endoscopy with 25 mg bevacizumab-800CW
A non-randomized, non-blinded, prospective, feasibility study.
- IV-administration of 25 mg of the fluorescent tracer bevacizumab-800CW to a total of 3 patients with locally advanced esophageal cancer. The optimal dose will be expanded to include 30 patients.
- Molecular fluorescence endoscopy: 2-3 days after administration, molecular fluorescence endoscopy will be performed with additional measurements of fluorescence signals.
干预措施: Molecular Fluorescence Endoscopy platform (Device)
结局指标
主要结局
Safety of bevacizumab-800CW administration by monitoring vital signs and/or (serious) adverse events.
时间窗: Up to 14 days after tracer injection
Monitoring vital signs (blood pressure, heart frequency and temperature) and/or (serious) adverse events that are related to the 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 endoscopy procedure
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 prior to and post neoadjuvant chemoradiotherapy, to identify patients who benefit from the chemoradiotherapy.
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)
- To localization and distribution of bevacizumab-800CW fluorescent signal at cell level observed in vivo by confocal laser endomicroscopy (CLE)(Up to 1,5 year)
- Assessment of the (sub)-cellular distribution of bevacizumab-800CW by ex vivo fluorescence microscopy(Up to 1,5 year)
- The variation in fluorescence intensity between fluorescence molecular endoscopy before and after neoadjuvant chemoradiotherapy defined as the tumor to background ratio and intrinsic fluorescence.(Up to 1,5 year)