Neoadjuvant Short-Course Radiotherapy Followed by Tislelizumab Combined With Chemotherapy for Locally Advanced Resectable Esophageal Squamous Cell Carcinoma: A Prospective, Multicenter, Exploratory Study
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Pathological Complete Response (pCR) Rate
研究概览
简要总结
Neoadjuvant Short-Course Radiotherapy Followed by Tislelizumab Plus Chemotherapy for Locally Advanced Resectable Esophageal Squamous Cell Carcinoma This is a prospective, randomized, two-arm, parallel-group, multicenter, exploratory Phase II clinical trial. It aims to evaluate the efficacy and safety of neoadjuvant short-course radiotherapy followed by tislelizumab combined with chemotherapy in participants with locally advanced resectable esophageal squamous cell carcinoma (ESCC).
Eligible participants will be randomized in a 1:1 ratio to receive either low-dose or high-dose short-course radiotherapy, followed by tislelizumab, nab-paclitaxel, and carboplatin for 3 cycles. Surgery will be performed 4-6 weeks after the last neoadjuvant treatment.
Primary endpoint: Pathological Complete Response (pCR) rate. Secondary endpoints: Major Pathological Response (MPR) rate, Objective Response Rate (ORR), R0 resection rate, downstaging rate, 3-year Event-Free Survival (EFS), 3-year Overall Survival (OS), safety profile, and quality of life.
Approximately 50 participants will be enrolled. Randomization will be stratified by tumor location, clinical T stage, and clinical N stage using a stratified block design via an EDC/IWRS system.
详细描述
Study Protocol Full Document Official Title Neoadjuvant Short-Course Radiotherapy Followed by Tislelizumab Combined With Chemotherapy for Locally Advanced Resectable Esophageal Squamous Cell Carcinoma: A Prospective, Multicenter, Exploratory Study Acronym SCR-TILES-ESCC Brief Summary This is a prospective, randomized, two-arm, parallel-group, multicenter, exploratory Phase II clinical trial. It aims to evaluate the efficacy and safety of neoadjuvant short-course radiotherapy followed by tislelizumab plus chemotherapy in participants with locally advanced resectable esophageal squamous cell carcinoma (ESCC). Eligible participants will be randomized 1:1 to receive low-dose or high-dose short-course radiotherapy, followed by 3 cycles of tislelizumab, nab-paclitaxel, and carboplatin. Surgery will be performed 4-6 weeks after the last neoadjuvant treatment. The primary endpoint is pathological complete response (pCR) rate. Secondary endpoints include major pathological response (MPR) rate, objective response rate (ORR), R0 resection rate, downstaging rate, 3-year event-free survival (EFS), 3-year overall survival (OS), safety, and quality of life. A total of 50 participants will be enrolled. Randomization will be stratified by tumor location, clinical T stage, and clinical N stage via an EDC/IWRS system using a stratified block design.
Detailed Description This is a prospective, randomized, two-arm, parallel-group, multicenter, exploratory Phase II clinical trial designed to evaluate the efficacy and safety of neoadjuvant short-course radiotherapy followed by tislelizumab combined with chemotherapy in participants with locally advanced resectable esophageal squamous cell carcinoma (ESCC).
- Study Rationale Neoadjuvant chemoradiotherapy followed by surgery is the standard of care for locally advanced esophageal cancer. However, recurrence remains high, and treatment-related toxicities may limit clinical application. Immunotherapy combined with chemotherapy has demonstrated promising pathological response rates in the neoadjuvant setting for ESCC. Radiotherapy can induce immunogenic cell death and enhance the anti-tumor effect of immune checkpoint inhibitors. This trial investigates a novel sequential strategy: short-course radiotherapy followed by tislelizumab plus chemotherapy, to optimize efficacy while minimizing perioperative complications.
- Study Design
This is a randomized, controlled, parallel-group Phase II study. Eligible participants will be randomized in a 1:1 ratio to two treatment groups via an electronic data capture (EDC) / interactive web randomization system (IWRS) using stratified block randomization. Stratification factors are:
Tumor location (upper thoracic esophagus / middle thoracic esophagus / lower thoracic esophagus) Clinical T stage (cT1-2 vs. cT3-4a) Clinical N stage (cN0 vs. cN+) Block size will be randomly set to 4 or 6 to ensure allocation concealment. Total planned enrollment: 50 participants. 3. Study Population Inclusion Criteria Voluntarily signed written informed consent. Age 18-75 years, inclusive. Expected survival ≥ 3 months. Clinically judged to be resectable with expected R0 resection. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. Histologically confirmed, treatment-naive, locally advanced resectable non-cervical esophageal squamous cell carcinoma: T1N1-3M0 or T2-4aN0-3M0 (T2 ≥3 cm or poorly differentiated).
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
- •Voluntarily provided written informed consent prior to any study-related procedures
- •Aged 18 to 75 years, male or female
- •Life expectancy of at least 3 months
- •Predicted to achieve R0 surgical resection
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Histologically confirmed, treatment-naive, resectable locally advanced thoracic esophageal squamous cell carcinoma (ESCC) meeting the staging criteria: T1 N1-3 M0 or T2-4a N0-3 M0 (T2 ≥3 cm or poorly differentiated). No suspected metastatic cervical lymph nodes (except for upper thoracic esophageal cancer regional lymph nodes) on neck ultrasound or contrast-enhanced CT, and no distant metastasis on imaging
- •Presence of measurable tumor lesions.
- •Adequate organ function defined by laboratory parameters: Absolute neutrophil count (ANC) ≥1.5×10⁹/L; platelet count ≥100×10⁹/L; hemoglobin ≥90 g/L. Total bilirubin ≤1.5×ULN; AST and ALT ≤2.5×ULN. Serum creatinine ≤1.5×ULN or calculated creatinine clearance ≥60 mL/min. INR ≤1.5, PT and APTT ≤1.5×ULN
- •Men and women of childbearing potential must use effective contraception during treatment and for 6 months after the last dose of study treatment
- •Good compliance and ability to complete scheduled follow-up.
排除标准
- •Prior treatment with PD-1/PD-L1 inhibitors or other immunomodulatory agents targeting T-cell receptors (e.g., CTLA-4, OX40)
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage
- •Active or suspected autoimmune disease, including systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, except type 1 diabetes controlled by replacement therapy, hypothyroidism, or skin disorders not requiring systemic therapy
- •History of grade ≥2 interstitial lung disease
- •Systemic corticosteroids (>10 mg prednisone daily or equivalent) or other immunosuppressive agents within 14 days before first study treatment
- •Primary or acquired immunodeficiency, organ transplantation, allogeneic hematopoietic stem cell transplantation
- •Live vaccine within 4 weeks before first study treatment
- •Severe uncontrolled cardiovascular or cerebrovascular disease: Uncontrolled hypertension or pulmonary hypertension. Unstable angina, myocardial infarction, coronary artery bypass grafting, or stent implantation within 6 months. NYHA class ≥2 chronic heart failure. Left ventricular ejection fraction (LVEF) <50%.
- •Clinically significant arrhythmia requiring treatment. Cerebrovascular accident (CVA) or transient ischemic attack (TIA) within 6 months. Uncontrolled active infection requiring systemic antibiotics. Positive HIV test, active hepatitis B or hepatitis C infection (exceptions: HBV DNA <500 IU/mL; HCV RNA undetectable).
- •Active pulmonary tuberculosis (TB). Other active malignancy within the previous 2 years, except adequately treated thyroid cancer, carcinoma in situ of the cervix, basal/squamous cell skin cancer, or ductal carcinoma in situ of the breast
- •History of drug abuse or psychiatric disorder
- •Pregnant or lactating women
- •Any other severe medical, psychiatric, or laboratory abnormality that, in the investigator's opinion, would increase study-related risk or interfere with result interpretation.
结局指标
主要结局
Pathological Complete Response (pCR) Rate
时间窗: Within 1 week after surgical resection.
The primary outcome measure is the rate of pathological complete response (pCR) after completion of neoadjuvant treatment. Pathological complete response is defined as the absence of residual invasive cancer cells in the primary esophageal tumor bed and all sampled regional lymph nodes, confirmed by postoperative pathological examination by a qualified pathologist.
次要结局
- Major Pathological Response(MPR) Rate(Within 1 week after surgical resection)
- R0 Resection Rate(At the time of surgical resection)
- Incidence of Treatment-Related Adverse Events (CTCAE v5.0)(From start of neoadjuvant treatment through 30 days after last study treatment)
- Objective Response Rate (ORR)(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to surgical resection)
- 3-Year Event-Free Survival (EFS) Rate(Followed up for up to 3 years from the date of randomization.)
- 3-Year Overall Survival (OS) Rate(Up to 3 years from randomization)
- Change in SF-36 Quality of Life Scale Score(Baseline prior to neoadjuvant therapy, Perioperative (after all neoadjuvant cycles before surgery), 3 months post-surgery, 6 months post-surgery, 12 months post-surgery)