Endoesophageal Cryotherapy: A New Technique For Ablating Barrett's Esophagus And Early Stage Esophageal Cancer
试验速览
- 阶段
- 4 期
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- Confirm the feasibility and safety of endoscopic cryotherapy in patients with Barrett's esophagus with LGD, HGD, intramucosal cancer and in patients with severe squamous dysplasia.
研究概览
简要总结
In this prospective single center study, up to 25 patients with Barrett's esophagus with LGD or no dysplasia (Group 1), 25 patients with HGD/IMCA (Group 2), 25 patients with esophageal carcinoma confined to the esophageal wall (Group 3) and 25 patients with severe esophageal squamous dysplasia (Group 4) will be treated with endoscopic cryotherapy. This study is single arm and no blinding will be utilized. Interim analysis of the data will be reviewed with a DCI statistician after 14 patients in each group have been treated with cryotherapy and if safety and efficacy is documented to that point in time, we will request the ability to extend the enrollment to a maximum allowable amount of 25 patients per group. The proposed study duration is seven years, allowing two years for patient enrollment and 5 years for post treatment follow-up. Study duration per patient will total approximately six years.
Patients with Barrett's esophagus with no dysplasia or low grade dysplasia (group 1) will be treated with cryotherapy at six week intervals until Barrett's mucosa is ablated or six treatments are administered. Patients with Barrett's HGD and IMCA or severe esophageal squamous dysplasia (groups 2 and 4) will be treated with cryotherapy at six-week intervals until Barrett's mucosa is ablated or six treatments are administered. More advanced mass lesions are typically more difficult to eradicate with ablative therapies and may progress faster than patients with IMCA, therefore, patients with more advanced cancer (group 3) will be treated every 2 weeks until the lesion is eradicated up to eight treatments.
After cryotherapy treatment is complete (i.e. the esophagus has re-epithelialized with normal squamous epithelium for Groups 1, 2, 4 and the tumor is locally controlled/absent in Group 3), patients will be assessed by endoscopy and biopsy every three months for one year, every six months for two years, then annually for two years (flow sheet - appendix 1; study schedule - appendix 2).
详细描述
Baseline evaluation will include the following ( all are considered standard of care except # 8 ):
- Informed consent.
- Evaluation of inclusion/exclusion criteria
- Demographics- date of birth, age, gender, ethnicity
- Medical history and physical exam
- Imaging (groups 2, 3 and 4) i. CT scan of the chest and abdomen with oral and intravenous contrast (if not allergic) ii. Endoscopic Ultrasound, with evaluation of the esophageal wall and mediastinum and upper abdomen for evidence of abnormal lymph nodes. Suspicious lymph nodes (round, hypoechoic, homogeneous, > 5mm) will undergo EUS-guided fine needle aspiration if appropriate, as deemed by the principal investigator.
- Pathology review (groups 2 and 4) - two independent reviewers, including at least one from the WRAMC Pathology Department, will review the pathology slides from esophageal biopsies. This review will serve to confirm the diagnosis of Barrett's esophagus with high grade dysplasia and/or IMCA for agreement of the diagnosis of adenocarcinoma and the degree of dysplasia.
- Presentation at Tumor Board prior to entering the protocol (groups 2, 3 and 4).
- Dysphagia score (see Appendix 4) is for research purposes.
Prior to cryotherapy:
As part of the research protocol, all patients will be treated with high dose proton pump inhibitor (PPI) (lansoprazole 30mg, esomeprazole 40mg, pantoprazole 40mg, omeprazole 40mg or rabeprazole 40mg) BID for maximal acid suppression until complete ablation is achieved or the patient exits the study. All of these agents are considered equally effective at the doses listed with no one agent considered superior. Treatment with these research doses will begin at least one week prior to the first cryotherapy session. Pre-enrollment standard doses of PPI will be restarted once the patient enters the surveillance phase or exits the study. Care will be taken to avoid, if possible, any potentially toxic medications to the esophageal mucosa (i.e. non-steroidal anti-inflammatory drugs, bisphosphonates, potassium supplements).
EGD/Cryotherapy Patients will be scheduled for EGD with cryotherapy on designated days when support for the cryotherapy device is available according to the study timeline (Appendix 2). A commitment from the CSA Medical Inc. (Baltimore, MD) will provide technical support for sessions to allow patients timely treatment.
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
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •** You must be eligible for care within the Department of Defense (DEERS eligible) to be enrolled into this protocol **
- •Per Groups 1,2,3,4 (above)
- •Specifically:
- •Diagnosis of specialized intestinal metaplasia (Barrett's esophagus) with either low grade, indeterminate or no dysplasia (Group 1)
- •high grade or intramucosal cancer and deemed inoperable based on co-morbid conditions such as severe heart, lung, kidney or liver disease; or refusal of surgical intervention; CT scan and EUS demonstrating no evidence of trans-mural tumor or lymph node involvement; pathology review of esophageal biopsies by 2 independent reviewers to include 1 from the Walter Reed Army Medical Center Pathology Department; presentation at tumor board (Group 2)
- •T1smN0 or T2NO adenocarcinoma arising in Barrett's esophagus and all criteria as for group 2 (Group 3)
- •diagnosis of severe squamous dysplasia and all criteria as for group 2 (Group 4)
排除标准
- •Not eligible for care within the Department of Defense medical system
- •Age less than 18 years or greater then 85 years (at time of entry)
- •Co-morbid illness expected to cause death within 6 months
- •Pregnancy (as determined by urine HCG)
- •Medically unfit or other contraindications to tolerate upper endoscopy
- •Inability to tolerate therapy with a proton pump inhibitor
- •Refusal or inability to give consent
结局指标
主要结局
Confirm the feasibility and safety of endoscopic cryotherapy in patients with Barrett's esophagus with LGD, HGD, intramucosal cancer and in patients with severe squamous dysplasia.
时间窗: These outcomes are measured at each endoscopy, with limits set on the number of procedures that can be done based on group assignment.
次要结局
- Assess the incidence of side effects, complications, adverse events and number of treatment sessions needed to reach primary endpoints.(Measured throughout the protocol during the treatment phase with cryotherapy.)