Biomarker Based Neoadjuvant Strategies for Locally Advanced Resectable Esophageal Squamous Cell Carcinoma: an Exploratory Phase II Single-arm Clinical Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Pathological Complete Response (pCR) Rate
研究概览
简要总结
This study aims to evaluate the impact of the neoadjuvant treatment strategy based on CPS score on the pathological complete response (pCR) rate in patients with resectable locally advanced esophageal cancer.
详细描述
Esophageal cancer is a malignant tumor with a high incidence in China, with most patients diagnosed at the advanced stage. Traditional treatment modalities include surgery, chemoradiotherapy, and chemotherapy. However, under current standard treatments, approximately 50% of patients remain incurable, primarily due to postoperative recurrence and distant metastasis. Therefore, seeking a new treatment strategy to improve efficacy is crucial.
This clinical trial aims to evaluate the use of immune checkpoint inhibitors in neoadjuvant therapy based on CPS scoring to enhance the pathologic complete response (pCR) rate. Patients pathologically confirmed with esophageal squamous cell carcinoma (ESCC) will undergo surgical assessment for operability. Eligible patients will further undergo CPS testing and will receive different neoadjuvant treatment strategies based on CPS results: patients with CPS ≥20 will receive neoadjuvant immunotherapy alone; CPS 10-20 patients will receive neoadjuvant chemotherapy followed by immunotherapy; and CPS <10 patients will receive standard neoadjuvant chemoradiotherapy.
After completing neoadjuvant therapy, patients will rest for 4-6 weeks before undergoing curative surgery, which will be reassessed by thoracic surgeons for R0 resection feasibility preoperatively. Postoperatively, pathological evaluation will assess the pCR rate and other secondary study endpoints, with the most severe toxicities included in the analysis.
This study anticipates a group-wide pCR rate of 45% based on a PD-L1 biomarker-guided neoadjuvant treatment strategy. The trial is designed to exclude a pCR rate of 30% or lower using a one-sided 95% confidence interval (α set at 0.025) and 80% statistical power, with a total sample size of 90. The null hypothesis will be rejected if fewer than 34 patients achieve pCR in the entire cohort.
Based on reference studies (EC-CRT-001, ESCORT-1, JUPITER-06, and KEYNOTE-590) and CPS distribution data for esophageal squamous cell carcinoma from our institution, it is expected that the proportions of patients with CPS ≥20, 10-20, and <10 will be 10%, 40%, and 50%, respectively, corresponding to 9, 36, and 45 eligible patients for each group. It is anticipated that biological specimens will be obtained from more than 30 patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Diagnosis: Histologically confirmed esophageal squamous cell carcinoma (ESCC).
- •Stage: Resectable locally advanced ESCC (clinical stage II-III according to the AJCC/UICC 8th edition).
- •Age: 18-75 years old.
- •Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •PD-L1 Expression: Available PD-L1 expression level (CPS).
- •Surgical Eligibility: Assessed as eligible for surgical resection by a thoracic surgeon.
- •Laboratory Requirements:
- •Adequate bone marrow function: Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L, Platelets ≥ 100 x 10^9/L, Hemoglobin ≥ 9 g/dL.
- •Adequate liver function: Total bilirubin ≤ 1.5 x upper limit of normal (ULN), AST and ALT ≤ 2.5 x ULN.
- •Adequate renal function: Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 60 mL/min.
- •Informed Consent: Ability to understand and willingness to sign a written informed consent document.
排除标准
- •Distant Metastasis: Presence of distant metastasis.
- •Other Malignancies: History of other malignancies within the past 5 years, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin carcinoma, or other localized non-invasive malignancy.
- •Autoimmune Diseases: History of active autoimmune diseases requiring systemic treatment within the past 2 years.
- •Infections: Active infection requiring systemic therapy.
- •Uncontrolled Conditions: Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Previous Treatment: Previous treatment with anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibodies.
- •Pregnancy and Lactation: Pregnant or breastfeeding women. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to randomization.
- •Allergies: Known allergy or hypersensitivity to study drugs or any excipient of these medications.
研究组 & 干预措施
High PD-L1 Expression Group (CPS ≥ 20)
Patients with high PD-L1 expression (CPS ≥ 20) will receive neoadjuvant immunotherapy alone. This treatment consists of serplulimab for 2 cycles.
干预措施: Serplulimab (Drug)
Moderate PD-L1 Expression Group (CPS 10-20)
Patients with moderate PD-L1 expression (CPS 10-20) will receive neoadjuvant chemotherapy combined with immunotherapy. This includes paclitaxel and cisplatin along with serplulimab for 2 cycles.
干预措施: Serplulimab (Drug)
Moderate PD-L1 Expression Group (CPS 10-20)
Patients with moderate PD-L1 expression (CPS 10-20) will receive neoadjuvant chemotherapy combined with immunotherapy. This includes paclitaxel and cisplatin along with serplulimab for 2 cycles.
干预措施: Paclitaxel+Cisplatin (Neoadjuvant Chemotherapy) (Drug)
Low PD-L1 Expression Group (CPS < 10)
Patients with low PD-L1 expression (CPS < 10) will receive standard neoadjuvant chemoradiotherapy. This includes paclitaxel and cisplatin along with radiotherapy (40 Gy in 20 fractions over 4 weeks).
干预措施: Paclitaxel+Cisplatin(Concurrent Chemoradiotherapy) (Drug)
Low PD-L1 Expression Group (CPS < 10)
Patients with low PD-L1 expression (CPS < 10) will receive standard neoadjuvant chemoradiotherapy. This includes paclitaxel and cisplatin along with radiotherapy (40 Gy in 20 fractions over 4 weeks).
干预措施: Radiotherapy (Radiation)
结局指标
主要结局
Pathological Complete Response (pCR) Rate
时间窗: after the pathological examination of surgical speciments within 14 days after the operation
The proportion of patients achieving a pathological complete response (pCR) after neoadjuvant treatment and surgical resection. pCR is defined as the absence of any residual invasive cancer in the resected esophagus and all sampled lymph nodes (ypT0N0) based on hematoxylin and eosin staining.
次要结局
- 3-Year Disease-Free Survival (DFS)(36 months after treatment completion)
- R0 Resection Rate(after the pathological examination of surgical speciments ie within 14 days after the operation)
- Treatment-Related Toxicity(From the start of treatment to 30 days post-surgery)
- Tumor Mutational Burden (TMB)(36 months after treatment completion.)
- Microsatellite Instability (MSI)(36 months after treatment completion)
- Circulating Tumor DNA (ctDNA)(36 months after treatment completion)
- major pathological response(Patients were evaluated 2 to 4 weeks postoperatively.)
研究者
Yong Yang
Principal Investigator
Fujian Medical University Union Hospital