A Phase Ib Study of Pre-Operative Pembrolizumab + Chemoradiation in Patients With Locally Advanced Esophageal Squamous Cell Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Safety (Number of Participants With Grade 3 and Higher-grade Treatment-related Adverse Events)
研究概览
简要总结
This study will evaluate the safety and feasibility of preoperative immune checkpoint therapy with concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma. And this study will provide valuable information for further clinical trials of preoperative pembrolizumab and other immune checkpoint therapy in esophageal cancer treatment.
详细描述
Esophageal cancer ranks the eighth most common cancer (the fifth most common cancer in China), while ESCC is the most common subtype in Asia (more than 90 % in china). Radical resection is thought to be the mainstay of esophageal cancer treatment and preoperative CRT is well applied in treating locally advanced esophageal cancer. In a multicohort, phase IB study, pembrolizumab was used in 23 unresectable esophageal cancer patients. In this clinical trial, the incidence of grade 3 treatment-related adverse events was 39 % without the appearance of grade 4 and higher-grade adverse event, while the overall response rate reached 30 %. The safety of immune checkpoint therapy for unresected esophageal cancers using nivolumab, a different PD-1 monoclonal antibody, has also been confirmed by high quality clinical trials.
This study will evaluate the safety and feasibility of preoperative immune checkpoint therapy using pembrolizumab with concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma. And this study will provide valuable information for further clinical trials of preoperative pembrolizumab and other immune checkpoint therapy in esophageal cancer.
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 1
Arm 1:preoperative pembrolizumab with chemoradiotherapy group Participants will receive carboplatin (AUC=2) IV and paclitaxel (50mg/m²) IV on day 1,8,15,22,29. And radiotherapy will start on day 1 of chemotherapy. A total of 41.4 Gy, 23 fractions of 1.8 Gy, 5 fractions a week. Participants will also receive pembrolizumab (2mg/kg) IV on days 1 and 22. Surgery will be performed within 6 weeks after completion of preoperative therapy described above.
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Safety (Number of Participants With Grade 3 and Higher-grade Treatment-related Adverse Events)
时间窗: From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose
The number of participants with grade 3 and higher-grade treatment-related adverse events. Adverse events were evaluated using CTCAE 4.0, grade 3 treatment-related adverse events and higher-grade adverse events were reported.
次要结局
- Radiographic Response(From date of treatment allocation and during treatment period up to 3 months)
- Feasibility (Number of Participants Who Finished Pembrolizumab With Chemoradiotherapy and Receive Surgery Within 4-6 Weeks After Preoperative Therapies)(From date of treatment allocation until surgery or definitive chemoradiotherapy was applied, whichever came first, assessed up to 5 months)
- Pathologic Complete Response(Two weeks after surgery)
研究者
Hecheng Li M.D., Ph.D
Professor
Ruijin Hospital