Node-Sparing Short-Course Radiotherapy (25 Gy/5 Fractions) Combined With Chemoimmunotherapy as Neoadjuvant Treatment for Locally Advanced Esophageal Squamous Cell Carcinoma：A Prospective Single-Arm, Phase II Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 33
- 试验地点
- 1
- 主要终点
- Pathologic Complete Response (pCR) Rate
研究概览
简要总结
This prospective, single-arm phase II study will evaluate the efficacy and safety of lymphatic-drainage-sparing short-course radiotherapy combined with camrelizumab and nab-paclitaxel/carboplatin as neoadjuvant treatment for patients with resectable, locally advanced thoracic esophageal squamous cell carcinoma. Participants will receive three 3-week cycles of camrelizumab plus chemotherapy, with 25 Gy in 5 fractions of short-course radiotherapy delivered to the primary tumor and radiographically positive lymph nodes while elective lymphatic drainage regions are spared. Definitive McKeown esophagectomy is planned 4-6 weeks after completion of neoadjuvant therapy. The primary endpoint is pathologic complete response (ypT0N0).
详细描述
The study is designed as a Simon optimal two-stage, single-arm phase II trial. The target sample size is 33 participants, allowing for approximately 10% attrition. In stage 1, 15 participants will be enrolled; if at least 4 achieve pathologic complete response, enrollment will proceed to stage 2. A further 15 evaluable participants will then be enrolled. The protocol considers the regimen promising if at least 15 of 30 evaluable participants achieve pathologic complete response.
Eligible participants are treatment-naive adults aged 18-75 years with PET-CT and pathologically confirmed thoracic esophageal squamous cell carcinoma, clinical stage cT1b-3N1-2M0 or cT2-3N0M0 (AJCC 9th edition), ECOG performance status 0-1, measurable disease by RECIST v1.1, and disease considered amenable to R0 resection.
Neoadjuvant treatment consists of camrelizumab 200 mg intravenously on Day 1 every 3 weeks plus nab-paclitaxel 260 mg/m² on Day 1 and carboplatin AUC 5 on Day 1 for three cycles. Short-course radiotherapy (25 Gy in 5 fractions over 5 days) is delivered after the first cycle, targeting only the primary tumor and positive lymph nodes and sparing elective lymphatic drainage regions. Tumor imaging is performed after the second cycle and before surgery. McKeown esophagectomy is planned 4-6 weeks after completion of neoadjuvant therapy when hematologic and organ function have recovered. Postoperative survival follow-up is planned every 3 months for 3 years.
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
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent before enrollment.
- •Age 18 to 75 years, any sex.
- •Treatment-naive esophageal squamous cell carcinoma confirmed by pathology and PET-CT.
- •Clinical stage cT1b-3N1-2M0 or cT2-3N0M0 (stage II/III according to the AJCC 9th edition).
- •Disease assessed as amenable to R0 surgical resection before treatment.
- •At least one measurable lesion according to RECIST v1.
- •ECOG performance status 0-
- •Adequate organ function: absolute neutrophil count ≥1,500/mm³; platelets ≥100,000/mm³; hemoglobin ≥9 g/dL; serum creatinine ≤1.5 mg/dL and/or creatinine clearance ≥60 mL/min; bilirubin ≤1.5×ULN; AST and ALT ≤1.5×ULN; no blood components or hematopoietic growth factors within 14 days.
- •For women of childbearing potential: medically accepted contraception during treatment and for 3 months afterward; negative serum or urine HCG within 7 days before enrollment; not breastfeeding.
- •For men who are not surgically sterile: agreement to use medically accepted contraception with their partner during treatment and for 3 months afterward.
- •Willingness to participate and comply with safety and survival follow-up.
排除标准
- •Prior radiotherapy, chemotherapy, prolonged/high-dose corticosteroid therapy, surgery, or molecular targeted therapy.
- •Previous or concurrent other malignancy.
- •Prior PD-1/PD-L1 therapy; known allergy to macromolecular protein preparations or any component of PD-1 therapy.
- •Active autoimmune disease or relevant autoimmune disease history as specified in the protocol.
- •Immunosuppressive agents for immunosuppression within 2 weeks before enrollment.
- •Symptomatic pleural or peritoneal effusion requiring therapeutic puncture or drainage.
- •Poorly controlled clinically significant cardiac disease as specified in the protocol.
- •Abnormal coagulation with bleeding tendency or thrombolytic/anticoagulant therapy.
- •Recent gastrointestinal conditions associated with bleeding or perforation risk.
- •Severe bleeding within 3 months, hemoptysis within 4 weeks, or thromboembolic event within 12 months according to protocol thresholds.
- •Active infection or unexplained fever >38.5°C during screening or before first dose.
- •Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks before study treatment.
- •History/current pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis, or severe pulmonary dysfunction.
- •Congenital/acquired immunodeficiency including HIV infection, or active hepatitis outside protocol-defined limits.
- •Participation in another clinical study or completion of a previous clinical study within 1 month; anticipated need for other systemic anticancer therapy.
- •Live vaccine within 4 weeks before study treatment or anticipated during the study.
- •Known history of psychotropic drug abuse, alcohol abuse, or illicit drug abuse.
- •Unable or unwilling to bear self-paid portions of study-related examinations or treatment.
- •Any other condition considered by the investigator to compromise participant safety, study completion, or data/sample collection.
研究组 & 干预措施
Neoadjuvant SCRT + Camrelizumab + Nab-Paclitaxel/Carboplatin
Participants receive three 3-week cycles of camrelizumab plus nab-paclitaxel and carboplatin. Lymphatic-drainage-sparing short-course radiotherapy (25 Gy in 5 fractions over 5 days) is delivered after the first cycle. McKeown esophagectomy is planned 4-6 weeks after completion of neoadjuvant treatment.
干预措施: Neoadjuvant SCRT + Camrelizumab + Nab-Paclitaxel/Carboplatin (Radiation)
结局指标
主要结局
Pathologic Complete Response (pCR) Rate
时间窗: At definitive surgery, approximately 4-8 weeks after completion of neoadjuvant therapy.
Percentage of participants undergoing definitive surgery who have no residual viable tumor in the resected primary tumor and regional lymph nodes, defined in the protocol as ypT0N0.
次要结局
- Major Pathologic Response (MPR) Rate(At definitive surgery, approximately 4-8 weeks after completion of neoadjuvant therapy.)
- Objective Response Rate (ORR)(From baseline to the preoperative tumor assessment, approximately 9-15 weeks after initiation of neoadjuvant therapy.)
- R0 Resection Rate(Upon completion of final postoperative pathological assessment, expected within 7 days post-operatively)
- Disease-Free Survival (DFS) Rate(1 year and 3 years after surgery.)
- Overall Survival (OS) Rate(1 year and 3 years after surgery.)
研究者
HONGYING_LIAO
Chief Physician, Department of Thoracic Surgery
Sixth Affiliated Hospital, Sun Yat-sen University