Phase III Multicenter Randomized Controlled Trial of PD-1 Inhibitor Combined With Preoperative Concurrent Chemoradiotherapy and Surgery for Locally Advanced Esophageal Squamous Cell Carcinoma (NEOCRTEC2101)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 422
- 试验地点
- 1
- 主要终点
- Overall survival
研究概览
简要总结
The primary objective is to compare PD-1 inhibitor combined with preoperative chemoradiotherapy followed by surgery versus neo-adjuvant chemoradiotherapy followed by surgery, in terms of the overall survival time (OS) in patients with Stage T1-4aN1-3M0 or T3-4aN0M0 squamous cell esophageal carcinoma.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologic diagnosis of squamous cell thoracic esophageal carcinoma of Stage T1-4aN1-3M0 or T3-4aN0M0,which is potentially resectable.
- •Patients must not have received any prior anticancer therapy.
- •More than 6 months of expected survival.
- •Age ranges from 18 to 70 years.
- •Absolute white blood cells count ≥4.0×109/L, neutrophil ≥1.5×109/L, platelets ≥100.0×109/L, hemoglobin ≥90g/L, and normal functions of liver and kidney.
- •WHO PS score 0-1
- •Signed informed consent document on file.
排除标准
- •Patients have received any prior anticancer therapy.
- •Patients are diagnosed or suspected to be allergic to sintilimab,toxal or cisplatin.
- •Patients with concomitant hemorrhagic disease.
- •Patients who cannot tolerate surgery.
- •Pregnant or breast feeding.
- •Patients without informed consent because of psychological, family, social or any other factors.
- •Patients with concomitant peripheral neuropathy, whose CTC status is 2 or even more.
- •Patients with malignant tumors other than esophageal cancer,except for non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer.
- •Patients with history of diabetes over 10 years and unsatisfactory glycemic control.
- •Patients with severe heart,lung,liver,renal dysfunction, hematopoietic system diseases, immune system diseases, cachexia or other diseases that lead to intolerance of chemoradiotherapy or surgery.
- •Patients with history of autoimmune diseases, immunodeficiency, or organ and allogeneic bone marrow transplantation.
- •Patients with history of interstitial lung disease or noninfectious pneumonia.
- •Patients with active pulmonary tuberculosis infection, or a history of active pulmonary tuberculosis infection within one year before enrollment, or a history of active pulmonary tuberculosis infection more than one year ago without regular treatment.
- •Patients with active hepatitis B ( HBV DNA ≥ 2000 IU / mL or 104 copies / mL ) or hepatitis C ( HCV antibody positive ).
研究组 & 干预措施
NCRT+IO group
• NCRT+IO group consists of the PD-1 inhibitor combined with concurrent chemoradiotherapy prior to surgery. The patient will receive 4 weeks of radiation therapy. The radiation will generally commence on the 1st day of treatment and will run for 4 weeks.PD-1 inhibitor is given by intravenous infusion on days 1 and 22. Chemotherapy is given by intravenous infusion on days 1, 8, 15, and 22.
Interventions:
- Radiation: (40 or 45 Gy/20 fractions)
- Drug: Sintilimab
- Drug: Paclitaxel
- Drug: Cisplatin
干预措施: Sintilimab (Drug)
NCRT+IO group
• NCRT+IO group consists of the PD-1 inhibitor combined with concurrent chemoradiotherapy prior to surgery. The patient will receive 4 weeks of radiation therapy. The radiation will generally commence on the 1st day of treatment and will run for 4 weeks.PD-1 inhibitor is given by intravenous infusion on days 1 and 22. Chemotherapy is given by intravenous infusion on days 1, 8, 15, and 22.
Interventions:
- Radiation: (40 or 45 Gy/20 fractions)
- Drug: Sintilimab
- Drug: Paclitaxel
- Drug: Cisplatin
干预措施: Preoperative radiotherapy (Radiation)
NCRT+IO group
• NCRT+IO group consists of the PD-1 inhibitor combined with concurrent chemoradiotherapy prior to surgery. The patient will receive 4 weeks of radiation therapy. The radiation will generally commence on the 1st day of treatment and will run for 4 weeks.PD-1 inhibitor is given by intravenous infusion on days 1 and 22. Chemotherapy is given by intravenous infusion on days 1, 8, 15, and 22.
Interventions:
- Radiation: (40 or 45 Gy/20 fractions)
- Drug: Sintilimab
- Drug: Paclitaxel
- Drug: Cisplatin
干预措施: Paclitaxel (Drug)
NCRT+IO group
• NCRT+IO group consists of the PD-1 inhibitor combined with concurrent chemoradiotherapy prior to surgery. The patient will receive 4 weeks of radiation therapy. The radiation will generally commence on the 1st day of treatment and will run for 4 weeks.PD-1 inhibitor is given by intravenous infusion on days 1 and 22. Chemotherapy is given by intravenous infusion on days 1, 8, 15, and 22.
Interventions:
- Radiation: (40 or 45 Gy/20 fractions)
- Drug: Sintilimab
- Drug: Paclitaxel
- Drug: Cisplatin
干预措施: Cisplatin (Drug)
NCRT group
• NCRT group consists of the concurrent chemoradiotherapy prior to surgery. The patient will receive 4 weeks of radiation therapy. The radiation will generally commence on the 1st day of treatment and will run for 4 weeks. Chemotherapy is given by intravenous infusion on days 1, 8, 15, and 22.
Interventions:
- Radiation: (40 or 45 Gy/20 fractions)
- Drug: Paclitaxel
- Drug: Cisplatin
干预措施: Paclitaxel (Drug)
NCRT+IO group
• NCRT+IO group consists of the PD-1 inhibitor combined with concurrent chemoradiotherapy prior to surgery. The patient will receive 4 weeks of radiation therapy. The radiation will generally commence on the 1st day of treatment and will run for 4 weeks.PD-1 inhibitor is given by intravenous infusion on days 1 and 22. Chemotherapy is given by intravenous infusion on days 1, 8, 15, and 22.
Interventions:
- Radiation: (40 or 45 Gy/20 fractions)
- Drug: Sintilimab
- Drug: Paclitaxel
- Drug: Cisplatin
干预措施: esophagectomy (Procedure)
NCRT group
• NCRT group consists of the concurrent chemoradiotherapy prior to surgery. The patient will receive 4 weeks of radiation therapy. The radiation will generally commence on the 1st day of treatment and will run for 4 weeks. Chemotherapy is given by intravenous infusion on days 1, 8, 15, and 22.
Interventions:
- Radiation: (40 or 45 Gy/20 fractions)
- Drug: Paclitaxel
- Drug: Cisplatin
干预措施: Preoperative radiotherapy (Radiation)
NCRT group
• NCRT group consists of the concurrent chemoradiotherapy prior to surgery. The patient will receive 4 weeks of radiation therapy. The radiation will generally commence on the 1st day of treatment and will run for 4 weeks. Chemotherapy is given by intravenous infusion on days 1, 8, 15, and 22.
Interventions:
- Radiation: (40 or 45 Gy/20 fractions)
- Drug: Paclitaxel
- Drug: Cisplatin
干预措施: Cisplatin (Drug)
NCRT group
• NCRT group consists of the concurrent chemoradiotherapy prior to surgery. The patient will receive 4 weeks of radiation therapy. The radiation will generally commence on the 1st day of treatment and will run for 4 weeks. Chemotherapy is given by intravenous infusion on days 1, 8, 15, and 22.
Interventions:
- Radiation: (40 or 45 Gy/20 fractions)
- Drug: Paclitaxel
- Drug: Cisplatin
干预措施: esophagectomy (Procedure)
结局指标
主要结局
Overall survival
时间窗: At end of enrollment- up to 5 years in follow up
Overall survival will be calculated from the date of randomization and an event registered on the date of death from any cause. Patients lost to follow up, or those with no death recorded on the day the database is frozen, will be censored on the date of last follow up.
次要结局
- Perioperative mortality(Ninety after surgery)
- Progression free survival(At end of enrollment- up to 5 years in follow up)
- Pathologic complete response rate(Two weeks after surgery)
- Incidence of perioperative complications(Ninety days after surgery)
- R0 resection rate(Two weeks after surgery)
研究者
Yang Hong
Prof.
Sun Yat-sen University