A Multicenter Randomized, Controlled Phase III Clinical Trial of Pembrolizumab Plus Paclitaxel and Cisplatin Versus Neoadjuvant Chemoradiotherapy Followed by Surgery for Locally Advanced Esophageal Squamous Cell Carcinoma (KEYSTONE-002)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 342
- 试验地点
- 1
- 主要终点
- Event Free Survival (EFS)
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of pembrolizumab plus paclitaxel, cisplatin as neoadjuvant therapy followed by surgery, and pembrolizumab as adjuvant therapy, compared with neoadjuvant chemoradiotherapy and surgery for locally advanced ESCC in multicenter.
详细描述
Preoperative chemoradiotherapy with radical surgery is the recommended treatment for locally advanced esophageal squamous cell carcinoma (ESCC) in the NCCN guidelines. But many patients refused or abandon radiotherapy because of the intolerable adverse effects. The purpose of this study is to evaluate the efficacy and safety of pembrolizumab plus paclitaxel, cisplatin as neoadjuvant therapy followed by surgery, and pembrolizumab as adjuvant therapy, compared with neoadjuvant chemoradiotherapy and surgery for locally advanced ESCC in multicenter. The primary study hypothesis is that Event Free Survival (EFS) is superior with pembrolizumab plus neoadjuvant chemotherapy compared with neoadjuvant chemoradiotherapy in participants with ESCC.
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
- •Histologically confirmed esophageal squamous cell carcinoma;
- •R0 resectable thoracic esophageal cancer, cT1-3N1-2M0, cT2-3N0M0 (AJCC V8 TNM classification);
- •No suspicious metastatic lymph nodes on the clavicle;
- •Have a performance status of 0 or 1 on the ECOG Performance Scale;
- •Age 18-75 years old, both men and women;
- •Be willing and able to provide written informed consent/assent for the trial;
- •Demonstrate adequate organ function ;
- •Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours before receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required;
- •Be willing to provide tissue, blood, and urine samples. Tissue should be from a newly obtained core or excisional biopsy of a tumor lesion through repeated biopsies. Newly-obtained is defined as a specimen obtained up to 4 weeks (28 days) before initiation of treatment on Day
- •Have not received systemic or local treatment for esophageal cancer in the past.
排除标准
- •Ineligibility or contraindication for esophagectomy;
- •Prior therapy (operation, radiotherapy, immunotherapy, or chemotherapy) for esophageal cancer
- •Active autoimmune disease or history of autoimmune disease;
- •Requiring systemic treatment with either corticosteroids or other immunosuppressive medications;
- •Subjects with a history of symptomatic interstitial lung disease;
- •History of allergy to study drug components;
- •Women must not be pregnant or breast-feeding;
- •Patient has received prior chemotherapy, radiotherapy, target therapy ，and immune therapy for this malignancy or any other past malignancy;
- •Underlying medical conditions that, in the Investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity or adverse events.
研究组 & 干预措施
Pembrolizumab+ Paclitaxel+Cisplatin+ Surgery+Pembrolizumab (228)
Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 every 3 weeks (Q3W), paclitaxel 135mg/m^2 IV on Day 2 Q3W, and cisplatin 80 mg/m^2 IV on Day 2 Q3W, a total of three cycles. All treatments will be beginning on Day 1 of each 3-week dosing cycle. Surgery should be done within 4-6 weeks after the last neoadjuvant treatment. After surgery, pembrolizumab 200 mg IV on Day 1 Q3W lasting one year.
Surgery: McKeown esophagectomy
干预措施: Pembrolizumab (Biological)
Pembrolizumab+ Paclitaxel+Cisplatin+ Surgery+Pembrolizumab (228)
Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 every 3 weeks (Q3W), paclitaxel 135mg/m^2 IV on Day 2 Q3W, and cisplatin 80 mg/m^2 IV on Day 2 Q3W, a total of three cycles. All treatments will be beginning on Day 1 of each 3-week dosing cycle. Surgery should be done within 4-6 weeks after the last neoadjuvant treatment. After surgery, pembrolizumab 200 mg IV on Day 1 Q3W lasting one year.
Surgery: McKeown esophagectomy
干预措施: Paclitaxel (Drug)
Pembrolizumab+ Paclitaxel+Cisplatin+ Surgery+Pembrolizumab (228)
Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 every 3 weeks (Q3W), paclitaxel 135mg/m^2 IV on Day 2 Q3W, and cisplatin 80 mg/m^2 IV on Day 2 Q3W, a total of three cycles. All treatments will be beginning on Day 1 of each 3-week dosing cycle. Surgery should be done within 4-6 weeks after the last neoadjuvant treatment. After surgery, pembrolizumab 200 mg IV on Day 1 Q3W lasting one year.
Surgery: McKeown esophagectomy
干预措施: Cisplatin (Drug)
neoadjuvant chemoradiotherapy+ Surgery (114)
neoadjuvant chemoradiotherapy 41.4Gy(1.8Gy×23 fractions) with five cycles of TP(Paclitaxel 50mg/m^2 on D1 and Cisplatin 25mg/m^2 D1, repeated every week. Surgery should be done within 4-6 weeks after the last neoadjuvant treatment.
Surgery: McKeown esophagectomy
干预措施: neoadjuvant chemoradiotherapy (Radiation)
结局指标
主要结局
Event Free Survival (EFS)
时间窗: Up to approximately 2.5 years
EFS is defined as the time from randomization to the first documented disease progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by investigator, or recurrence, or metastasis, or death due to any cause, whichever occurs first. For this analysis, EFS will be assessed in participants with ESCC.
次要结局
- Overall Survival (OS)(3 and 5 years)
- Disease Free Survival (DFS)(3 and 5 years)
- Major pathologic response (MPR)(1 month after resection)
- Objective response rate (ORR)(1 month after resection)
- Pathologic Complete Response (PCR)(1 month after resection)
- assessment in perioperation(perioperative period)
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability](up to 16 months)
- Quality of life differences (EORTC QLQ-C30)(2.5 years)
- Quality of life differences (EORTC QLQ-OES18)(2.5 years)