Neoadjuvant Immunotherapy Combined With Neoadjuvant Chemotherapy for Locally Advanced Esophageal Cancer: an Open Label, Randomized Control, Phase II Trial
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Major Pathological Response (MPR) rate
研究概览
简要总结
Currently, surgery after neoadjuvant chemoradiotherapy is the standard treatment for patients with locally advanced esophageal cancer, but the recurrence rate is high and the 5-year survival rate is low. Immunotherapy shows a potential treatment for esophageal cancer. Immunocheckpoint (PD-1/PD-L1) inhibitors can activate tumor immunity. The guidelines have recommended it as a sencond-line therapy. However, there is still lack of the evidence for its efficacy as a neoadjuvant therapy. This study is to conduct a randomized controlled, open label, phase II clinical trial to evaluate the efficacy and safety of neoadjuvant immnotherapy combined with neoadjuvant chemotherapy for locally advanced esophageal squamous cell carcinoma (ESCC) patient with PD-L1 (CPS>=10%) positive.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Volunteer to participated and sign information consent;
- •Age 18-70, male or female;
- •Locally advanced esophageal cancer diagnosed by pathology, Clinical tumor stage should be II-IVa; tumor located at the lower middle segment;
- •No previous chemoradiotherapy or immunotherapy;
- •PD-L1 expression >=10%;
- •Have a performance status of 0 or 1 on the ECOG Performance Scale;
- •Demonstrate adequate organ function as defined below (excluding the use of any blood components and cytokines during the screening period): Absolute neutrophil count (ANC) ≥1.5*109 /L; Platelet ≥100*109/L; Hemoglobin ≥ 9 g/dL; Serum albumin≥3g/dL; Bilirubin≤1.5 x ULN; ALT and AST≤2.5 ULN; Serum creatinine ≤1.5 x ULN or creatinine clearance ≥40mL/min; LVEF>=50%; Urine protein<++; INR<1.5 and APTT<1.5;
- •Female subject must have taken reliable contraceptive measures of childbearing potential should have a negative urine or serum pregnancy within 7 days prior to receiving the first dose of study medication. and be willing to use an appropriate method of contraception during the trial and 8 weeks after the last administration of the test drug. Male subject should agree to use appropriate contraceptive methods or to have been surgically sterilized during the trial and 8 weeks after the last administration of the test drug.
排除标准
- •Any active autoimmune disease or history of autoimmune disease (as follows, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitritis, vasculitis, nephritis, hyperthyroidism, thyroid dysfunction);
- •Asthma requiring medical intervention with bronchodilators was not included.
- •Subjects with history of severe allergy;
- •There are clinical symptoms or diseases of the heart that are not well controlled, such as: heart failure above grade 2 by the Criteria of NYHA; unstable angina pectoris; myocardial infarction occurred within 1 year; Clinically meaningful supraventricular or ventricular arrhythmias require treatment or intervention;
- •Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), or has known active Hepatitis B (e.g. HBV DNA≥ 2000IU/ml or copy number ≥104/ml;) or Hepatitis C (e.g. HCV antibody positive);
- •Systematic glucocorticoid therapy is administered one week prior to neoadjuvant therapy;
- •Subjects who are participating other drug clinical trials.
研究组 & 干预措施
intervention group
Neoadjuvant immunotherapy (PD-1) plus concurrent chemotherapy (paclitaxel + Cisplatin) will be applied to patients with locally advanced esophageal squamous cell carcinoma with PD-L1>=10% before surgery.
干预措施: Sintilimab Injection plus Paclitaxel and Cisplatin (Drug)
controll group
Neoadjuvant chemotherapy (paclitaxel + Cisplatin) will be applied to patients with locally advanced esophageal squamous cell carcinoma with PD-L1>=10% before surgery.
干预措施: Paclitaxel and Cisplatin (Drug)
结局指标
主要结局
Major Pathological Response (MPR) rate
时间窗: 30 days after the second cycle of treatment(each cycle is 21 days)
MPR is defined as 10% or fewer viable cancer cells in the hematoxylin and eosin (H\&E)-stained slides from the resected tumor following neoadjuvant treatment.
次要结局
- 2-year progression-free survival (PFS)(every 3 months (up to 24 months))
- Objective Response Rate (ORR)(at the end of the second cycle of treatment(each cycle is 21 days))
- The incidence of adverse events(the day from the first treatment cycle)
研究者
Sang Shaowei
Associate Professor
Qilu Hospital of Shandong University