The Efficacy of Neoadjuvant PD-1 Plus Concurrent Chemotherapy for Stage II-IVA Operable Esophageal Squamous Cell Carcinoma：A Single Armed, Open-label, Multicentre, Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- Pathologic complete remission (PCR)
研究概览
简要总结
This study aims to evaluate the efficacy of Camrelizumab plus concurrent chemotherapy as neoadjuvant approach for patients with opearble esophageal squamous cell carcinoma. In addition, potential clinical utility of ctDNA in monitoring tumor burden and dynamics of tumor clonality during neoadjuvant immunotherapy will be assessed as well. At the same time, CD8 and PD-L1 will also be used as monitoring indicators.
详细描述
Immunotherapy improves clinical outcome of patients with advanced stage or metastatic esophageal squamous cell carcinoma (ESCC). In addition, superior effect of immunotherapy for esophageal squamous cell carcinoma was also reported recently. While, clinical application of ctDNA, PD-L1 and CD8 T cell monitoring in neoadjuvant immunotherapy for patients with esophageal squamous cell carcinoma is largely unknown. This trial will evaluate firstly the efficacy and the safety of Camrelizumab plus chemotherapy （albumin-bound paclitaxel plus cisplatin）as neoadjuvant approach. The evaluation indicators include pathological complete response rate (pCR) and objective imaging response rate after neoadjuvant therapy (ORR). ), 2-year progression-free survival (2y-PFS), postoperative progression-free survival (PFS), and overall survival (OS) after treatment. Objective response rate (ORR) based upon immune-Response Evaluation Criteria in Solid Tumors Version (RECIST v1.1). Major pathological response assessed by post-operational pathological review ctDNA efficacy will also be evaluated along with clinical management. Monitoring tumor burden, clonality as well as tumor heterogeneity evaluation will be correlated to radiological assessment and pathological findings.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 17 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female patients aged ≥18 years, ≤70 years.
- •Gastroscope/ultrasound gastroscopy biopsy, Histologically or cytologically confirmed esophageal squamous cell carcinoma. Clinically diagnosed as II-IVA esophageal squamous cell carcinoma (cT2N1-3M0/cT3N0-3M0/cT4N0-3M0).
- •Non-Cervical Esophageal Cancer
- •Previously received no systemic or topical treatment for esophageal cancer, at least one measurable lesion for neoadjuvant treatment imaging evaluation according to RECIST 1.1;
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Estimated survival time ≥ 12 months;
- •Subjects had no major organ dysfunction, and the investigators assessed thyroid, lung, liver, kidney function, and cardiac function as normal.
- •Women of childbearing age must have taken reliable Contraception or have the negative predictive value of urine/ serum pregnancy test within 7 days prior to enrollment. They are also willing to use appropriate methods of contraception during the trial and 8 weeks after the last administration of the test drugs. For men, They must agree to use contraception or surgical sterilization during the trial and 8 weeks after the last administration of the test drug.
- •Subjects voluntarily joined the study and signed informed consent. patients who accept blood sample collection at multiple time points. Able to comply with the required protocol and follow-up procedures, and able to receive oral medications.
排除标准
- •Have a history of gastrectomy or have surgical contraindications
- •The investigator assessed that the patient had other serious illnesses that may affect follow-up and short-term survival;
- •There are any active autoimmune diseases or a medical history of autoimmune (including, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, thyroid function Decreased. Subjects with vitiligo or adults who have had childhood asthma but have fully relieved without any intervention may be included. However, subjects who require bronchodilators for medical intervention cannot be included.)
- •Cardiac clinical symptoms or diseases that are not well controlled, such as: a. Heart Failure NYHA > Class Ⅱ, b. unstable angina, c. myocardial infarction within 1 year; d. Clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention.
- •Subjects with congenital or acquired immunodeficiency (such as HIV-infected), or active hepatitis (hepatitis B reference: HBsAg-positive, HBV DNA ≥ 2000 IU/ml or copy number ≥ 104/ml; hepatitis C reference: HCV antibody-positive.)
- •Uncontrollable history of diabetes;
- •Patients who have used other clinical trial study drugs within 4 weeks prior to the first dose.
- •Severe allergic reactions to monoclonal antibodies or allergy to paclitaxel or human albumin.
- •Peripheral blood neutrophil count is less than 1500/mm3
- •Patients who have received or are undergoing other chemotherapy, radiation therapy or targeted therapy.
- •According to the investigator's assessment, there are other factors that may lead to the termination of the study, such as other serious diseases (including mental illness) requiring combined treatment. Any other condition and social/psychological problems, etc., the investigator judged that the patient was not suitable for participation in the study.
研究组 & 干预措施
camrelizumab plus concurrent chemotherapy
Neoadjuvant immunotherapy, PD-1, plus concurrent chemotherapy（albumin-bound paclitaxel + Cisplatin） will be applied to patients with operable esophageal squamous cell carcinoma before surgery.
干预措施: camrelizumab (Drug)
camrelizumab plus concurrent chemotherapy
Neoadjuvant immunotherapy, PD-1, plus concurrent chemotherapy（albumin-bound paclitaxel + Cisplatin） will be applied to patients with operable esophageal squamous cell carcinoma before surgery.
干预措施: Paclitaxel for injection (albumin-bound) (Drug)
camrelizumab plus concurrent chemotherapy
Neoadjuvant immunotherapy, PD-1, plus concurrent chemotherapy（albumin-bound paclitaxel + Cisplatin） will be applied to patients with operable esophageal squamous cell carcinoma before surgery.
干预措施: Cisplatin (Drug)
结局指标
主要结局
Pathologic complete remission (PCR)
时间窗: 4 weeks after surgery
Primary tumor or lymph node surgery specimen pathological examination without residual tumor cell
次要结局
- Objective Response Rate (ORR)(At the end of Cycle 2 (each cycle is 21 days))
- 2-year progression-free survival (PFS)(every 2 months (up to 24 months))
- Progression-free survival (PFS)(every 2 months (up to 24 months))
- Overall survival (OS)(every 2 months (up to 24 months))
研究者
Jun Liu
Clinical professor, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University
Guangzhou Institute of Respiratory Disease