Multicenter Preoperative Anti-PD-1 Antibody Combined With Chemoradiotherapy for Locally Advanced Squamous Cell Carcinoma of Esophageus
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 143
- 试验地点
- 2
- 主要终点
- Pathologic complete response
研究概览
简要总结
To investigate the safety and activity of preoperative pembrolizumab combined with chemoradiotherapy for resectable esophageal squamous cell carcinoma (ESCC) ,20 patients enrolled in Phase Ib PALACE-1(NCT03792347).The results showed that preoperative pembrolizumab with concurrent chemoradiotherapy was safe, did not delay surgery and induced a pCR in 55.6% of resected tumors. In this multicentre prospective study(PALACE-2),the investigators will evaluate the efficacy of preoperative pembrolizumab with concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma.
详细描述
For locally advanced esophageal squamous cell carcinoma (ESCC), neoadjuvant chemoradiotherapy followed by surgery has been recommended as the optimal therapeutic strategy.Patients who achieved pathologic complete response(pCR) after receiving neoadjuvant therapy were more likely to have better survival. And the pCR rates was 43.2% reported in NEOCRTEC5010 trial, 49% with ESCC in the CROSS trial and 33.3% in FFCD 990130.
In Phase Ib PALACE-1(NCT03792347), the investigators firstly present that preoperative pembrolizumab combined with chemoradiotherapy followed by surgery is safe.All 20 patients have received PPCT successfully, except 1 patient who missed the last dose of chemotherapy due to leukopenia. Grade 3 and higher adverse events (AEs) were observed in 13 patients (13/20, 65%), and 1 patient had a grade 5 AE. The most frequent grade 3 AE was lymphopenia (12/13, 92%). Eighteen patients underwent surgery within 4-9 weeks after PPCT and the pCR rate was 55.6% (10/18).
This study (PALACE-2) will evaluate the efficacy of preoperative pembrolizumab with concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma in multicentres.
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
- •A patient will be eligible for inclusion in this study only if ALL of the following criteria apply:
- •Histologically confirmed cT2-T4a,N0-N+,M0 resectable esophageal squamous cell carcinoma.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •Patients approve and sign the informed consent
排除标准
- •Patients with active autoimmune disease or history of autoimmune disease.
- •Patients who have a condition 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.
- •Men with female partners (WOCBP) that are not willing to use contraception.
- •Patient has received prior chemotherapy, radiotherapy, target therapy and immune therapy for this malignancy or for 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
Arm A
Arm 1:
A: Pembrolizumab 200mg(100mg if weight less than 50kg) IV on days 1 and 22 B: Carboplatin (AUC=2) IV and paclitaxel (50mg/m²) IV on day 1,8,15,22,29. C: Radiotherapy will start on day 1 of chemotherapy. A total of 41.4 Gy, 23 fractions of 1.8 Gy, 5 fractions a week.
D: Ivor-Lewis or McKeown esophagectomy
The participants will receive preoperative A+B+C. 4-6 weeks after completion of preoperative therapy ，D will be performed if there is no contraindication.
干预措施: Pembrolizumab Injection (Drug)
结局指标
主要结局
Pathologic complete response
时间窗: 1 month after resection
Pathologic complete response was defined as pT0N0M0
次要结局
- 3-year disease free survival(3 years after resection)
- Overall Survival (OS)(5 years)
研究者
Hecheng Li M.D., Ph.D
Chair of thoracic department
Ruijin Hospital