Phase 2 Randomized Trial Of Liquid Nitrogen Spray Cryotherapy Prior To Neoadjuvant Systemic Therapy In Locally Advanced Esophageal Adenocarcinoma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Complete response (CR) rates
研究概览
简要总结
This research study is for people who have locally advanced esophageal adenocarcinoma and are expected to receive chemotherapy. The purpose of this study is to compare the effectiveness of Liquid Nitrogen Spray Cryotherapy (LNSC) in addition to chemotherapy versus chemotherapy alone in the treatment of esophageal adenocarcinoma. LNSC is an FDA approved device that works by using liquid nitrogen to rapidly cool cancerous tissue causing cell damage. Participants in this study will be randomly assigned to either the "LNSC group" or the "No-LNSC group." Participants in the "LNSC group" will undergo 2 sessions of LNSC through an upper endoscopy. Participants in the "No-LNSC group," may undergo an endoscopy if needed for symptoms such as difficulty swallowing. Participation in the research will last about 4 months.
详细描述
People with locally advanced esophageal adenocarcinoma (a type of cancer in the esophagus) often have trouble swallowing because of the tumor's size and spreading to nearby areas. Doctors diagnose and stage the cancer using upper endoscopy, cross-sectional imaging, and endoscopic ultrasonography. Management of locally advanced esophageal adenocarcinoma usually involves more than one type of therapy. Treatment often includes chemotherapy and surgical resection in operable cases. Studies show that complete response (CR) rates are low with neoadjuvant therapy for esophageal cancer. For example, pathologic CR (PCR) to neoadjuvant chemoradiation (CROSS) occurs in only 25-30% of people with locally advanced esophageal cancer. CR strongly correlates with overall survival in esophageal cancer. Therefore, additional neoadjuvant therapies/regimens are required to improve survival for people with this type of cancer.
Liquid nitrogen spray cryotherapy (LNSC) is a treatment for destroying abnormal tissue in Barrett's esophagus (BE) and esophageal cancer (EC). During LNSC, liquid nitrogen is sprayed through a thin tube that is passed through the working channel of a gastroscope. Liquid nitrogen rapidly cools neoplastic tissue to extremely low temperatures (-78°C to -196°C), causing intracellular ice formation. The freezing process leads to cell membrane rupture, protein denaturation, and microvascular thrombosis. This leads to cell death (necrosis) of the abnormal tissue.
Liquid Nitrogen Spray Cryotherapy (LNSC) may increase CR by boosting the body's immune response, which helps to fight and destroy the tumor cells. It is FDA-approved for debulking esophageal cancer. In a prospective multi-center study, it was found that LNSC caused minimal side effects and improves Quality of Life (QoL) in people with esophageal cancer that cannot have surgery and who were receiving systemic therapy. In a pilot clinical trial, it was found that LNSC resulted in a long-term CR rate of 56% when a single session of LNSC was administered prior to CROSS. When compared to matched participants who received CROSS alone, immune cells that fight tumor cells multiplied more frequently with LNSC + CROSS. Investigators then conducted a neoadjuvant LNSC dose frequency escalation trial. There was improved QoL and no severe (grade 3) side effects with two sessions of neoadjuvant LNSC. Consistent with our prior study, 64% of people who completed at least two sessions of LNSC had a clinical complete CR (CCR) after CROSS. These findings support the need for a larger study to investigate whether adding LNSC can improve treatment of locally advanced esophageal cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 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
- •Adults with locally advanced EAC who are expected to receive FLOT +/-Durvalumab will be eligible to participate.
- •Locally advanced esophageal cancer is defined as TNM stages T1N+M0 or T2-T4aNanyM0, as defined by endoscopic ultrasound (EUS) and PET-CT.
排除标准
- •Inability to pass the orogastric decompression tube into the stomach
- •Coagulopathy (INR > 2 or platelet count < 50,000 per cubic millimeter)
- •Inability to provide informed consent
- •Eastern Cooperative Oncology Group (ECOG) performance status > 2
- •Risk of thrombosis is determined to be too high to hold anti-platelets (other than aspirin) or anticoagulants prior to the procedure.
研究组 & 干预措施
Liquid Nitrogen Spray Cryotherapy (LNSC) + Standard of care chemotherapy
Participants will receive a standard of care chemotherapy, neoadjuvant FLOT +/- durvalumab WITH LNSC.
干预措施: LNSC (Procedure)
Liquid Nitrogen Spray Cryotherapy (LNSC) + Standard of care chemotherapy
Participants will receive a standard of care chemotherapy, neoadjuvant FLOT +/- durvalumab WITH LNSC.
干预措施: Standard of care chemotherapy (Other)
Standard of care chemotherapy
Participants will receive a standard of care chemotherapy, neoadjuvant FLOT +/- durvalumab WITHOUT LNSC.
干预措施: Standard of care chemotherapy (Other)
结局指标
主要结局
Complete response (CR) rates
时间窗: At treatment discontinuation, up to 12 weeks
CR is defined as the absence of tumor on re-staging scans and explant or mucosal biopsies (if applicable).
次要结局
- Change in systemic immune response(Baseline, 4 weeks post-chemotherapy, up to 16 weeks)
- Change in minimal residual disease (MRD)(Week 4 of chemotherapy, 2-4 weeks post-chemotherapy (up to 16 weeks))
- Overall survival (OS)(1 year)
- Change in dysphagia(Baseline, up to 2 weeks)
- Change in quality of life (QoL)(Baseline, up to 2 weeks)
- LNSC-related adverse events(30 days post-treatment, up to 20 weeks)