Fluorescence Molecular Endoscopy and Molecular Fluorescence-guided Surgery of Locally Advanced Rectal Cancer Using Cetuximab-IRDye800CW: a Single-center Feasibility and Safety Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Safety of molecular fluorescence endoscopy using Cetuximab-800CW
研究概览
简要总结
Treatment of patients with locally advanced rectal cancer (LARC) is multidisciplinary and consists of neoadjuvant chemoradiotherapy (nCRT) followed by surgical removal of the rectal tumor and potentially tumor positive lymph nodes.
- After surgery, in 15 to 27% of patients that received nCRT no tumor cells can be detected during histopathological examination. In today's clinical practice, all of these patients with a pathological complete response (pCR) are operated upon, with substantial morbidity and mortality. The 5-year survival is 83.3% for patients with a pCR, and 65.6% for those without pCR. Response after nCRT is currently evaluated using magnetic resonance imaging (MRI). However, as MRI cannot differentiate between molecular characteristics of tissue, prediction of treatment response can be inaccurate. In patients with a potential cCR on MRI, additionally a high-definition white-light (HD-WL) endoscopy is performed with biopsies of the previous tumor location. If both MRI and HD-WL endoscopy confirm a potential cCR, patients can also be treated with a watch-and-wait approach, including frequent follow-up with HD-WL endoscopy and MRI. This potentially prevents extensive surgical procedures for patients in which this is not required. However, MRI and HD-WL endoscopy often remain insufficient for identification of cCR. Therefore, novel imaging methods are needed for accurate prediction of treatment response in order to select patients. The investigators believe fluorescence molecular endoscopy (FME) could be a promising technique for evaluation of treatment response.
- During surgery, tumor-negative resection margins are of great prognostic value. Currently, surgeons rely on visual and tactile inspection for differentiation between malignant and healthy tissue. When in doubt, a frozen section can be obtained, which is time consuming and poses a high risk of sampling error. However, 14.7% of patients still have tumor-positive resection margins, increasing the risk of local recurrence and worsening outcome. Therefore, there is a need for novel imaging techniques that can be used intraoperatively to improve margin assessment. The investigators believe molecular fluorescence-guided surgery (MFGS) could be a promising technique for evaluation of resection margins.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 rectal cancer, in multi-disciplinary colorectal oncology meeting agreed on long course neoadjuvant chemoradiotherapy, followed by surgical removal of the primary tumor;
- •Clinical suspicion of residual tumor after neoadjuvant chemoradiotherapy;
- •Age ≥ 18 years;
- •Written informed consent.
排除标准
- •Medical or psychiatric conditions that compromise the patient's ability to give informed consent;
- •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);
- •Received an investigational drug within 30 days prior to the dose of cetuximab- IRDye800CW;
- •History of infusion reactions to cetuximab or other monoclonal antibodies;
- •Had within 6 months prior to enrollment: myocardial infarction, cerebrovascular accident, uncontrolled cardiac heart failure, significant liver disease, unstable angina pectoris;
- •Patients receiving Class IA (quinidine, procainamide) or Class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents;
- •Evidence of QT prolongation on an ECG made within three months prior to inclusion (greater than 440 ms in males or greater than 450 ms in females);
- •Magnesium, potassium and calcium deviations that might lead to cardiac rhythm (grade II or higher deviations by CTCAE), determined within three months prior to inclusion.
研究组 & 干预措施
NIR endoscopy and surgery with cetuximab-IRDye800CW
In this non-randomized, non-blinded, prospective, feasibility study, cetuximab-IRDye800CW will be administered to a total of 15 patients with proven locally advanced rectal cancer
干预措施: Cetuximab-IRDye800 (Drug)
NIR endoscopy and surgery with cetuximab-IRDye800CW
In this non-randomized, non-blinded, prospective, feasibility study, cetuximab-IRDye800CW will be administered to a total of 15 patients with proven locally advanced rectal cancer
干预措施: Fluorescent molecular endoscopy and surgery (Device)
结局指标
主要结局
Safety of molecular fluorescence endoscopy using Cetuximab-800CW
时间窗: up to 3 months
Number of participants with treatment-related (serious) adverse events
Safety of molecular fluorescence-guided surgery using Cetuximab-800CW
时间窗: up to 3 months
Number of participants with treatment-related (serious) adverse events
Feasibility of molecular fluorescence endoscopy using Cetuximab-800CW
时间窗: up to 3 months
Feasibility will be evaluated by assessing real-time during endoscopy whether fluorescence can be visualized and by taking images during fluorescence molecular endoscopy. Thereafter the fluorescence intensity using the raw data will be measured and a tumor-to-background ratio will be calculated.
Feasibility of molecular fluorescence-guided surgery using Cetuximab-800CW
时间窗: up to 3 months
Feasibility will be evaluated by assessing whether fluorescence can be detected in the resection margins and on the specimen. Thereafter the fluorescence intensity using the raw data will be measured and a tumor-to-background ratio will be calculated.
次要结局
- Evaluation of the distribution of Cetuximab-IRDye800CW(up to 3 months)
- Correlation of the fluorescent signal to histopathology and immunohistochemistry(up to 3 months)
- Quantifcation of the fluorescent signals(up to 3 months)