Early Response-guided Sequential Radiotherapy After Chemoimmunotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma: A Phase II Clinical Study
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 110
- 试验地点
- 1
- 主要终点
- Safety and Tolerability Equivalent Major Pathological Response Rate (ITT-MPR)
研究概览
简要总结
Esophageal squamous cell carcinoma (ESCC) is a common and aggressive malignancy with poor prognosis, particularly in patients with locally advanced disease. Neoadjuvant chemoimmunotherapy has shown promising antitumor activity and may improve pathological response; however, a proportion of patients achieve only stable disease (SD) or progressive disease (PD) after initial treatment and may have limited benefit from proceeding directly to surgery.
This prospective, single-center, phase II clinical study aims to evaluate an early response-guided sequential selective radiotherapy strategy after neoadjuvant chemoimmunotherapy in patients with locally advanced, resectable ESCC. Patients will initially receive neoadjuvant chemotherapy combined with PD-1 inhibitor therapy. Based on radiological response assessment, patients with major response (complete response or partial response) will proceed directly to radical surgery, whereas patients with insufficient response (stable disease or progressive disease but still considered resectable) will receive sequential chemoradiotherapy followed by surgery.
The study aims to assess the safety and efficacy of this individualized treatment strategy, with primary evaluation focusing on pathological response, surgical outcomes, and treatment-related adverse events. Exploratory analyses will investigate potential biomarkers associated with treatment response and prognosis.
详细描述
Esophageal squamous cell carcinoma (ESCC) is a major subtype of esophageal cancer and remains associated with poor outcomes, particularly in patients with locally advanced disease. Neoadjuvant chemoimmunotherapy has recently emerged as a promising treatment approach for resectable ESCC, improving tumor response and pathological remission. However, a subset of patients demonstrates limited response after initial therapy, and optimal management strategies for these patients remain uncertain.
Radiotherapy may enhance antitumor immune responses through modulation of the tumor microenvironment and may provide additional tumor control in patients with insufficient response to initial systemic therapy. Therefore, an individualized treatment strategy guided by early treatment response may help optimize therapeutic benefit while preserving opportunities for curative surgery.
This study evaluates an early response-guided sequential selective radiotherapy strategy for patients with locally advanced resectable ESCC after neoadjuvant chemoimmunotherapy. Treatment decisions will be adapted according to early tumor response assessment and multidisciplinary evaluation, aiming to provide additional local treatment for patients with inadequate response while avoiding unnecessary radiotherapy in patients with favorable response.
The study will assess the safety, feasibility, and clinical outcomes of this response-guided approach. In addition, exploratory analyses will investigate potential biomarkers associated with treatment response and prognosis, including changes in the tumor immune microenvironment and peripheral blood biomarkers.
This study aims to develop a personalized treatment strategy for locally advanced ESCC based on early therapeutic response and to improve clinical outcomes through optimized treatment selection.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must meet all of the following criteria:
- •Provide written informed consent before enrollment.
- •Age >18 years, male or female.
- •Histologically confirmed thoracic esophageal squamous cell carcinoma (ESCC).
- •Locally advanced, resectable disease according to AJCC/UICC 8th edition TNM staging system, defined as:
- •cT3-4aN0-2M0 or cT1-2N1-2M0;
- •No evidence of distant metastasis;
- •Considered initially resectable by a multidisciplinary surgical team.
- •Patients who have received neoadjuvant chemoimmunotherapy and have measurable disease response assessment according to RECIST v1.1, including complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD).
- •At least one measurable lesion according to RECIST version 1.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Expected survival time >6 months.
- •Adequate organ function meeting the following criteria:
- •Bone marrow function:
- •Absolute neutrophil count ≥1,500/mm³;
- •Platelet count ≥100,000/mm³;
- •Hemoglobin ≥9 g/dL.
- •Renal function:
- •Serum creatinine ≤1.5 mg/dL and/or creatinine clearance ≥60 mL/min.
- •Hepatic function:
- •Total bilirubin ≤1.5 × upper limit of normal (ULN);
- •AST and ALT ≤1.5 × ULN.
- •Participants of childbearing potential must agree to use medically approved contraception during study treatment and for 3 months after completion of treatment. Female participants of childbearing potential must have a negative serum or urine pregnancy test within 7 days before enrollment and must not be breastfeeding.
- •Willingness and ability to comply with study procedures, safety assessments, and survival follow-up.
排除标准
- •Participants will be excluded if any of the following criteria apply:
- •Evidence of distant metastasis.
- •Previous or concurrent malignancy, except adequately treated basal cell carcinoma of skin or cervical carcinoma in situ.
- •Previous thoracic radiotherapy.
- •Previous treatment with PD-1, PD-L1, or CTLA-4 inhibitors, or known hypersensitivity to PD-1 inhibitors or macromolecular protein products.
- •Active autoimmune disease or history of clinically significant autoimmune disease requiring systemic treatment.
- •Current use of immunosuppressive therapy or systemic corticosteroids exceeding the equivalent of prednisone 10 mg/day within 2 weeks before enrollment.
- •Clinically significant ascites or pleural effusion requiring therapeutic drainage.
- •Uncontrolled cardiovascular disease, including:
- •NYHA class II or higher heart failure;
- •Unstable angina;
- •Myocardial infarction within 1 year;
- •Clinically significant arrhythmias requiring treatment.
- •Significant coagulation abnormalities, bleeding tendency, or ongoing thrombolytic/anticoagulant therapy.
- •Active gastrointestinal disorders associated with bleeding or perforation risk, including esophageal varices, active gastric/duodenal ulcer, ulcerative colitis, portal hypertension, or active tumor bleeding.
- •History of severe bleeding, clinically significant hemoptysis, or thromboembolic events within specified periods.
- •Active infection or unexplained fever >38.5°C before treatment initiation.
- •Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks before study treatment.
- •History or evidence of interstitial lung disease, pulmonary fibrosis, radiation pneumonitis, drug-induced pneumonitis, pneumoconiosis, or severe pulmonary impairment.
- •Known immunodeficiency, including HIV infection, or active hepatitis infection requiring exclusion according to protocol criteria.
- •Participation in another clinical trial within 1 month before enrollment or concurrent systemic anticancer therapy.
- •Receipt of live vaccines within 4 weeks before treatment or planned live vaccination during study treatment.
- •Known history of substance abuse, alcoholism, or drug abuse.
- •Inability or unwillingness to comply with study-related procedures, examinations, or required costs.
- •Any other medical, psychological, social, or safety-related condition judged by the investigator to make the participant unsuitable for study participation.
结局指标
主要结局
Safety and Tolerability Equivalent Major Pathological Response Rate (ITT-MPR)
时间窗: Up to approximately 1.5 years
次要结局
- R0 Resection Rate(At the time of surgery after completion of neoadjuvant treatment)
- Surgical Completion Rate(At the time of surgery after completion of neoadjuvant treatment)
- Pathological Complete Response (pCR) Rate(At the time of 1 month after resection)
- Tumor Regression Grade (TRG)(At the time of surgery after completion of neoadjuvant treatment)
- Pathological Lymph Node Status (ypN0 Rate)(At the time of surgery after completion of neoadjuvant treatment)
- Tumor Downstaging Rate(At the time of surgery after completion of neoadjuvant treatment)
- Objective Response Rate (ORR)(After completion of neoadjuvant treatment before surgery (approximately 12 weeks after initiation of study treatment))
- Disease Control Rate (DCR)(After completion of neoadjuvant treatment before surgery)
- Treatment-related Adverse Events(From initiation of study treatment until 30 days after completion of treatment)
- Perioperative Complications(Within 30 days after surgery)