Stereotactic Body Radiotherapy Followed by Tislelizumab Plus Platinum-based Chemotherapy Versus Tislelizumab Plus Platinum-based Chemotherapy as Neoadjuvant Therapy in Patients With Resectable Stage Ⅱ-Ⅲ Non-small Cell Lung Cancer: A Phase Ⅲ, Randomized, Multicenter, Prospective Study
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 360
- 试验地点
- 1
- 主要终点
- event-free survival
研究概览
简要总结
The goal of this clinical trial is to compare the efficacy and safety of neoadjuvant Stereotactic Body Radiotherapy (SBRT) combined with immunochemotherapy versus neoadjuvant immunochemotherapy. The main questions it aims to answer are:
Dose SBRT combined with immunochemotherapy improve event-free survival? Is SBRT combined with immunochemotherapy safe enough?
Participants will:
Receive neoadjuvant SBRT combined with immunochemotherapy or neoadjuvant immunochemotherapy.
Tumor assessment will be performed prior to surgery. Surgery will be performed within 4 to 6 weeks (+ 7 days) after completion of the last cycle of immunochemotherapy.
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
- •Patients voluntarily agree to participate and sign the informed consent;
- •Patients with cytologically/histologically diagnosed (by means of percutaneous lung aspiration biopsy, bronchoscopy, mediastinoscopy, etc.), untreated stage IIa-IIIa (according to the AJCC 8th edition of thoracic tumor staging) non-small cell lung cancer. In addition, patients with potentially resectable stage IIIb (T3-4N2) NSCLC will also be enrolled. All patients are required to receive PET/CT (or chest + upper abdominal CT + brain MRI) at baseline for clinical staging;
- •Pulmonary lesions will be assessed as resectable/potentially resectable by a multiple disciplinary team including thoracic surgeon;
- •Eastern Cooperative Oncology Group Performance Status 0 to 1
- •Requirements for hematology: i, neutrophils ≥ 1500 x 109/L; ii, platelets ≥ 100 x 109/L; iii, hemoglobin > 9.0 g/dL; iv, serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min; v, aspartate transaminase (AST)/alanine transaminase (ALT) ≤ 3 x ULN; vi, total bilirubin ≤ 1.5 x ULN; vii. forced expiratory volume in the first second (FEV1) ≥ 1.2 L or > 40% predicted; viii. International Normalized Ratio/activated partial thromboplastin time (INR/APTT) within the normal range;
排除标准
- •Patients with or suspected with autoimmune diseases. Note: patients with vitiligo, type 1 diabetes, hypothyroidism managed with hormone replacement therapy only (Hashimoto's thyroiditis) can be enrolled in the study when there is no clear evidence of recurrence;
- •Patients required systemic corticosteroids treatment (dose > 10 mg daily prednisolone [or equivalent]) or other immunosuppressive drugs within 14 days of enrollment. Note: inhaled or topical corticosteroids, or adrenal replacement therapy (dose > 10 mg daily prednisolone [or equivalent]) are acceptable for patients without apparent autoimmune disease;
- •Historical radiotherapy of chest
- •Active bleeding before treatment
- •Patents with sever heart, lung, liver, or kidney insufficiency
- •Diabetes more than 10-year; unsatisfactory blood glucose control
- •Patients with interstitial lung disease or non-infectious pneumonia
- •EGFR-mutations and ALK-fusion positive NSCLC
- •Patients with other prior malignancies (except skin malignancies other than non-melanoma, and carcinoma in situ at the following sites [bladder, stomach, colorectal, endometrium, cervix, melanoma, or breast]) are not eligible for enrollment in this study. However, if the prior malignancies remain in complete response (CR) for ≥ 2 years and no additional anti-cancer therapy is required during the study, such patients are permitted to be enrolled;
- •The patient is medically, psychologically, or physiologically unable to complete the study or to understand the Patient Information Sheet, in the opinion of the investigator;
- •Received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA any other drugs specifically targeting T-cell co-stimulation or immunoregulation pathways;
- •Present active hepatitis B or hepatitis C
- •Patients with positive HIV test results or diagnosed with acquired immunodeficiency disease (AIDS);
- •Hypersensitivity to the investigational product;
- •Pregnant or lactating women.
研究组 & 干预措施
neoadjuvant SBRT combined with immunochemotherapy
Following admission, intrapulmonary primary stereotactic body radiotherapy (SBRT) was administered at a dosage of 24 Gy across three fractions. Subsequently, within seven days of completing SBRT, two cycles of Tislelizumab in combination with a platinum-based double-agent chemotherapy regimen were initiated. These cycles were repeated every three weeks. Surgical intervention was scheduled to occur 4-6 weeks (±7 days) after the completion of the second chemotherapy cycle
干预措施: Stereotactic body radiotherapy (SBRT) (Radiation)
neoadjuvant SBRT combined with immunochemotherapy
Following admission, intrapulmonary primary stereotactic body radiotherapy (SBRT) was administered at a dosage of 24 Gy across three fractions. Subsequently, within seven days of completing SBRT, two cycles of Tislelizumab in combination with a platinum-based double-agent chemotherapy regimen were initiated. These cycles were repeated every three weeks. Surgical intervention was scheduled to occur 4-6 weeks (±7 days) after the completion of the second chemotherapy cycle
干预措施: Tislelizumab (Drug)
neoadjuvant SBRT combined with immunochemotherapy
Following admission, intrapulmonary primary stereotactic body radiotherapy (SBRT) was administered at a dosage of 24 Gy across three fractions. Subsequently, within seven days of completing SBRT, two cycles of Tislelizumab in combination with a platinum-based double-agent chemotherapy regimen were initiated. These cycles were repeated every three weeks. Surgical intervention was scheduled to occur 4-6 weeks (±7 days) after the completion of the second chemotherapy cycle
干预措施: Chemotherapy (Drug)
neoadjuvant immunochemotherapy
Three cycles of Tislelizumab in conjunction with platinum-based chemotherapy were administered at three-week intervals. Surgical intervention was subsequently scheduled to occur within 4 to 6 weeks (±7 days) following the completion of the third chemotherapy cycle.
干预措施: Tislelizumab (Drug)
neoadjuvant immunochemotherapy
Three cycles of Tislelizumab in conjunction with platinum-based chemotherapy were administered at three-week intervals. Surgical intervention was subsequently scheduled to occur within 4 to 6 weeks (±7 days) following the completion of the third chemotherapy cycle.
干预措施: Chemotherapy (Drug)
结局指标
主要结局
event-free survival
时间窗: 5 years
include 2/3/5 event-free survival time
次要结局
- major pathologic response (MPR) rate(1-year)
- pathological complete response (PCR) rates(1-year)
- R0-resection rate(1-year)
- overall survival(5 years)
- safety(1-year)
研究者
Yang Hong
professor
Sun Yat-sen University