A Phase II, Prospective, Single-center, Randomized, Controlled Study to Investigate the Efficacy and Safety of Sintilimab or Placebo in Combination With Chemotherapy as Second-line Treatment for Patients With Stage IV Nonsquamous Non-small Cell Lung Cancer With Wild-type EGFR After Failure With Platinum-Containing Chemotherapy
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Compare Overall Survival (OS) between sintilimab +chemotherapy and placebo + chemotherapy.
研究概览
简要总结
This prospective, single-center, randomized, controlled study will evaluate the efficacy and safety of sintilimab or placebo in combination with chemotherapy as second-line treatment for patients with stage IV nonsquamous non-small cell lung cancer with wild-type EGFR after failure with platinum-containing chemotherapy. Treatment may continue as long as participants are experiencing clinical benefit as assessed by the investigator, i.e., in the absence of unacceptable toxicity or symptomatic deterioration attributed to disease progression.
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
- •Volunteer to participate in clinical research; fully understand and know the research and sign informed consent;
- •Age ≥ 18 years old and ≤ 75 years old, either sex;
- •Eastern Collaborative Oncology Group Performance status (ECOG PS) 0, 1 or 2;
- •Has a histologically or cytologically confirmed diagnosis of stage IV (according to the 8th edition of the International Association for the Study of Lung Cancer) nonsquamous NSCLC;
- •Have at least one measurable lesion as defined by RECIST 1.1;
- •Has progression of disease after treatment with at least two cycles of a platinum-containing doublet chemotherapy according to RECIST V.1.1;
- •Patients without activating EGFR mutation;
- •Normal hepatic function: total bilirubin≤1.5×normal upper limit (ULN); Alanine aminotransferase and Aspartate aminotransferase levels ≤2.5×ULN or ≤5×ULN if liver metastasis is present;
- •Normal renal function: Creatinine ≤1.5×ULN or calculated creatinine clearance ≥45 mL/min (using Cockcroft/Gault formula to calculate );
- •Normal hematological function: absolute neutrophil count ≥1.5×109/L, platelet count ≥70×109/L, hemoglobin≥80g/L [no blood transfusion or erythropoietin (EPO) within 7 days] Dependency];
- •Has a life expectancy of at ≥3 months.
排除标准
- •ECOG PS >2;
- •Small cell lung cancer and squamous NSCLC;
- •EGFR mutation or mutation status unknown;
- •Known hypersensitivity or allergy to monoclonal antibody;
- •Prior therapy with an anti-programmed cell death (PD)-1, anti-PD-L1, anti-PD-L2, anti-tumor necrosis factor CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways);
- •Active autoimmune disease, or a documented history of autoimmune disease;
- •Treatment with systemic corticosteroids (prednisone≥10mg per day or equivalent dose) or other systemic immunosuppressive medications within 2 weeks prior to the first dose;
- •Known history or active human immunodeficiency virus (HIV);
- •Known acute or chronic active hepatitis B (HBV DNA positive) infection or acute or chronic active hepatitis C (HCV antibody positive and HCV RNA positive) infection;
- •Interstitial lung disease, or history of pneumonitis requiring systemic steroids for treatment;
- •Active or poorly controlled severe infection;
- •Have serious cardiovascular disease: Symptomatic congestive heart failure (New York Heart Association grade III-IV), unstable angina pectoris, unstable arrhythmia, myocardial infarction or cerebrovascular accident within 3 months before randomization;
- •Received thoracic radiation therapy of >30 Gy within 6 months prior to first dose of study drug;
- •Completed palliative radiotherapy within 7 days prior to first dose of study drug;
- •Pregnant or lactating women.
研究组 & 干预措施
Sintilimab plus chemotherapy
Sintilimab (200 mg) plus chemotherapy (physicians' choice between docetaxel and pemetrexed) every 3 weeks.
干预措施: Sintilimab (Drug)
Sintilimab plus chemotherapy
Sintilimab (200 mg) plus chemotherapy (physicians' choice between docetaxel and pemetrexed) every 3 weeks.
干预措施: Docetaxel (Drug)
Sintilimab plus chemotherapy
Sintilimab (200 mg) plus chemotherapy (physicians' choice between docetaxel and pemetrexed) every 3 weeks.
干预措施: Pemetrexed (Drug)
Placebo plus chemotherapy
Placebo plus chemotherapy (physicians' choice between docetaxel and pemetrexed) every 3 weeks.
干预措施: Docetaxel (Drug)
Placebo plus chemotherapy
Placebo plus chemotherapy (physicians' choice between docetaxel and pemetrexed) every 3 weeks.
干预措施: Pemetrexed (Drug)
Placebo plus chemotherapy
Placebo plus chemotherapy (physicians' choice between docetaxel and pemetrexed) every 3 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Compare Overall Survival (OS) between sintilimab +chemotherapy and placebo + chemotherapy.
时间窗: approximately 24 months
To compare the efficacy of the combination of sintilimab and chemotherapy versus placebo and chemotherapy in terms of overall survival (OS) in patients with stage IV nonsquamous non-small cell lung cancer with wild-type EGFR after failure with platinum-containing chemotherapy. Overall Survival (OS) was defined as the time from the date of randomization to the date of death due to any cause. Data for participants who were not reported as dead at the time of analysis was censored at the date when they were last known to be alive.
次要结局
- Compare duration of response between sintilimab +chemotherapy and placebo + chemotherapy.(approximately 24 months)
- Compare objective response rate between sintilimab +chemotherapy and placebo + chemotherapy.(approximately 24 months)
- Compare Progression Free Survival (PFS) between sintilimab +chemotherapy and placebo + chemotherapy using RECIST 1.1.(approximately 24 months)
- Number of Participants who Experience Treatment Related Adverse Events (AEs).(approximately 24 months)
研究者
Xin-Hua Xu
professor
China Three Gorges University, Yichang, China