Optical PD-1 and PD-L1 Imaging Using Dual-wavelength Quantitative Fluorescence Endoscopy in Locally Advanced Esophageal Cancer Using Durvalumab-680LT and Nivolumab-800CW
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 15
- 主要终点
- Feasiblity
研究概览
简要总结
Radiation and chemotherapy can shrink the tumor. For certain types of cancer, immunotherapy is added to further reduce the tumor size. Immunotherapy works for some patients and can sometimes keep the cancer under control for a long time. Unfortunately, immunotherapy does not work for every patient. That's why researchers around the world are looking for new ways to predict who will benefit from immunotherapy and who will not.
It is likely that immunotherapy is more effective when the tumor or immune cells have specific targets, such as the proteins PD-L1 or PD-1. Unfortunately, clinicians cannot reliably detect these proteins through blood tests or tissue samples, because their presence can vary throughout the tumor.
With this study, the investigators hope to use a new technique called 'fluorescence endoscopy' during an endoscopic ultrasound of the esophagus to visualize whether the PD-L1 or PD-1 proteins are present in esophageal cancer or immune cells. Additionally, the investigators aim to investigate whether the presence of these proteins changes before and after chemotherapy and/or radiation. This will help us determine the best timing for measuring these proteins in the future.
What is fluorescence endoscopy? To determine whether the proteins are present, participants in this study will receive two 'tracers' via an IV beforehand. The first tracer is a fluorescent substance-a kind of 'glow-in-the-dark' compound-attached to a drug that binds to PD-L1 proteins in esophageal cancer. The second fluorescent tracer binds to PD-1 proteins on immune cells.
During fluorescence endoscopy, the investigators use special equipment to detect these tracers in the esophagus. This information may help us better identify which patients are suitable for immunotherapy treatment and which are not.
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
- Other
- 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
- •Lesion suspected for locally advanced EC (cT1b-4a N0-3 M0);
- •Indication for neoadjuvant therapy or definitive chemo-radiation therapy;
- •Age ≥ 18 years;
- •Written informed consent.
排除标准
- •Medical or psychiatric conditions that compromise the patient's ability to give informed consent according to treating medical physician;
- •Concurrent uncontrolled medical conditions according to treating medical physician;
- •Medical history of auto-immune disease and on active treatment;
- •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 the primary tumor prior to start of neoadjuvant therapy according to the patient's medical history;
- •Received an investigational drug within 30 days prior to the tracer administration according to the patient's medical history;
- •History of infusion reactions to durvalumab or nivolumab or other monoclonal antibodies according to the patient's medical history;
研究组 & 干预措施
25 mg durvalumab-680LT + 15 mg nivolumab-800CW in esophageal cancer
干预措施: Spectroscopy system (Device)
25 mg durvalumab-680LT + 15 mg nivolumab-800CW in esophageal cancer
干预措施: Nivolumab-800CW (Drug)
25 mg durvalumab-680LT + 15 mg nivolumab-800CW in esophageal cancer
干预措施: Durvalumab-680LT (Drug)
25 mg durvalumab-680LT + 25 mg nivolumab-800CW in esophageal cancer
干预措施: Spectroscopy system (Device)
25 mg durvalumab-680LT + 25 mg nivolumab-800CW in esophageal cancer
干预措施: Nivolumab-800CW (Drug)
25 mg durvalumab-680LT + 25 mg nivolumab-800CW in esophageal cancer
干预措施: Durvalumab-680LT (Drug)
结局指标
主要结局
Feasiblity
时间窗: Up to 14 months
To determine the feasibility of our newly built dual-wavelength spectroscopy system in combination with the fluorescent tracers durvalumab-680LT and nivolumab-800CW. The spectroscopy system is considered feasible if at least 4 out of 10 patients demonstrate a higher tumor-to-healthy tissue ratio based on spectroscopy measurements. This ratio is calculated by dividing the spectroscopy value of the tumor region by that of the adjacent healthy tissue. The threshold of 4 out of 10 patients was selected based on literature data, which indicate that approximately 43.5% to 48.1% of patients exhibit high PD-1/PD-L1 expression in the tumor area. The investigators therefore expect a similar proportion of patients to show elevated spectroscopy values corresponding to increased target expression.
Safety of dual tracer administratio
时间窗: Up to 14 months
• To assess the safety of dual tracer administration of nivolumab-800CW and durvalumab-680LT by evaluating heart rate in beats per minute.
次要结局
- Correlation between in vivo signal and ex vivo pathology(Up to 14 months)
- Investigate the sub-cellular location of the drugs.(Up to 14 months)
- Safety of dual tracer administration(Up to 14 months)
- Correlation of fluorescence intensity before and after neoadjuvant therapy(Up to 14 months)
- Correlation between in vivo signal and ex vivo analysis(Up to 14 months)
- Optimal dose determination of nivolumab-800CW(up to 12 months)