Multi-center Prospective Randomized Controlled Clinical Trial of Postoperative Adjuvant Chemotherapy, Adjuvant Radiotherapy, or Surgery Alone for High-risk Histological Node Negative Patients With Thoracic Esophageal Squamous Cell Carcinoma
试验速览
- 阶段
- 3 期
- 入组人数
- 486
- 试验地点
- 1
- 主要终点
- Disease free survival
研究概览
简要总结
Histological Node Negative thoracic esophageal squamous cell carcinoma（pN0 ESCC） after radical resection still carries the risk of recurrence after complete surgical resection, especially in some high-risk patients. There are still lack of knowledge on postoperative treatment indication and methods for pN0 ESCC.Our previous study has shown that risk of recurrence is associated with the location and cell differentiation of primary tumor, as well as the presence of lymphovascular invasion. This project is designed to study the efficacy of adjuvant therapies for at patients with pN0 ESCC and above mentioned risk factors of recurrence after radical surgery. We aim to compare the differences among adjuvant chemotherapy, adjuvant radiotherapy, and surgery alone for pN0 ESCC by prospective randomized controlled trial. There has been no similar studies in esophageal cancer previously reported with similar design. The results of this study is expected to have a high clinical relevance.
详细描述
The study is designed to be a prospective randomized controlled trial, aiming to compare the impact of adjuvant chemotherapy with Paclitaxel and Cisplatin, adjuvant radiotherapy with IMRT of 50Gy, and surgery alone on the disease free survival (DFS) of patients with high-risk pN0 thoracic esophageal squamous cell carcinoma. Pathological staging is to be based on the 7th UICC edition, after radical resection and systemic lymph node dissection,for accurate staging.Patients with pT1b-T4a disease, proved to be pN0 upon pathological examination, meet at least one of the risk factors in the inclusion criteria, and without any exclusion criteria are to be randomized into one of the three study arms.Definition of high-risk factors for recurrence include: (1)Tumor location: in the middle or upper third thoracic esophagus; (2) Presence of LVI or submucosal metastasis; (3) Cell differentiation: poorly differentiated or undifferentiated.
Primary endpoint:
To observe and compare Disease-Free Survivals (DFS) among the three study arms.
Secondary endpoint:
To observe and compare Overall Survivals (OS) among the three study arms, and to compare adverse events between adjuvant chemotherapy and adjuvant radiation groups.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient: No pretreatment before surgery.Informed consent signed after screening;
- •Surgery: Complete (R0) resection of tumor, with thoraco- abdominal two-field or cervico-thoraco-abdominal three-field lymph node dissection through transthoracic esophagectomy. At least 12 stations and 12 lymph nodes should be harvested, including bilateral recurrent laryngeal nerve nodes. Both open thoracotomy and minimally invasive thoracoscopic/laparoscopic approaches are allowed and histopathological examination confirmed the diagnosis of the patients with at least cleaning more or equal to 12 stations and 12 lymph nodes;
- •Histology: Thoracic esophageal squamous cell carcinoma, with no nodal involvement (pN0) after pathological examination;
- •Staging: Tumor T stage T1b-T4a according to the 7th UICC esophageal cancer staging system;
- •Definition of high risk for recurrence: meet at least one of the three below.
- •A: Primary tumor located in middle or upper third of thoracic esophagus
- •B: Presence of lymphovascular invasion (LVI) or submucosal metastasis
- •C: Cell differentiation:Low grade or undifferentiated
- •Performance status: ECOG score 0-2;
- •Cardiac function:NYHA classification 1-
- •Normal electrocardiogram;
- •Renal function: Normal serum creatinine level (SCr = 120mol/L) and creatinine clearance rate (CCr = 60 ml/min);
- •Hepatic function: Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) level less than or equal to 2.0 times the upper limit of normal (ULN). Serum alkaline phosphatase (ALP) level less than or equal to four times the upper limit of normal value. Serum total bilirubin level less than or equal to 1.5 times the upper limit of the normal value;
- •Hematopoietic function: White blood cell count (WBC) equal to or more than 4000 / μL,neutrophils (ANC) absolute count is more than or equal to 1500 / μ L, platelet count more than or equal to 100000/ μ L, hemoglobin equal to or more than 10.0 g / dl.
排除标准
- •Surgery through Left thoracic or transhiatal approach, whereby complete lymphadenectomy is not achieved;
- •Patients experienced severe postoperative complication and thus, are unable to tolerate any adjuvant therapy;
- •Patients who have concommitant other malignant tumor;
- •Patients with abnormal coagulation function, with bleeding tendencies (such as active peptic ulcer) or are currently receiving thrombolysis or anticoagulation therapies;
- •Severe cardiac comorbidities, including congestive heart failure,uncontrolled cardiac arrhythmia, unstable angina pectoris, myocardial infarction within six months,severe heart valve disease, or intractable hypertension;
- •Severe hepatic or renal insufficiency;
- •Poor mental status or mental disorders, poor compliance.
研究组 & 干预措施
Adjuvant chemotherapy group
Surgery followed by adjuvant chemotherapy,with Paclitaxel and Cisplatin.
干预措施: Adjuvant chemotherapy (Paclitaxel and Cisplatin) (Drug)
Adjuvant radiotherapy group
Surgery followed by 50Gy adjuvant radiotherapy
干预措施: Adjuvant radiotherapy (Radiation)
Control group
Surgery alone
干预措施: Control group (Surgery alone) (Other)
结局指标
主要结局
Disease free survival
时间窗: 3 years
次要结局
- Overall survival(5 years)
- side effect of adjuvant therapy(6 months)
研究者
Wentao Fang
Chief Director,Clinical Center of Esophageal Diseases,Shanghai Jiao tong University
Shanghai Chest Hospital