Minimal Residual Disease (MRD)-Guided Adjuvant Therapy in Stage I Non-Small Cell Lung Cancer: A Prospective, Multicenter, Randomized Controlled Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 342
- 试验地点
- 15
- 主要终点
- 3-Year disease-free survival (DFS) Rate
研究概览
简要总结
This investigator-initiated study aims to evaluate the effectiveness of minimal residual disease (MRD) as a biomarker for guiding adjuvant therapy decisions in patients with Stage I non-small-cell lung cancer (NSCLC). The study will compare outcomes between an MRD-guided management group and a standard-of-care group, focusing on whether the use of MRD information can improve the 3-year disease-free survival rate compared to existing treatment protocols. Participants in the MRD-guided management group will receive targeted therapy, immunotherapy, or observation based on their postoperative MRD status, while those in the standard-of-care group will receive treatments or observation according to current clinical guidelines.
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
- •Non-small cell lung cancer (NSCLC) confirmed by histological and/or cytological examination. Invasive subtypes are required for adenocarcinomas.
- •Stage IA or IB after surgery based on pathological TNM8 staging criteria established by the International Union Against Cancer/American Joint Committee on Cancer (8th Edition).
- •Completely surgical resection (R0) of the primary NSCLC via lobectomy, segmentectomy, or sleeve lobectomy. The gross tumor must be entirely removed, and all surgical margins of the excised tumor must be negative.
- •Complete recovery from surgery with no evidence of disease progression within 2 weeks prior to the first treatment decision.
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0-
- •Minimum life expectancy of ≥12 weeks.
- •Demonstrate adequate organ function, including:
- •Hematological parameters:
- •Absolute neutrophil count ≥1.5×10^9/L
- •Platelet count ≥100×10^9/L
- •Hemoglobin ≥90 g/L
- •Liver function:
- •ALT ≤2.5× upper limit of normal (ULN)
- •AST ≤2.5×ULN
- •Total Bilirubin (TBL) ≤1.5×ULN Renal function: Creatinine level ≤1.25×ULN, or creatinine clearance ≥60 mL/min (measured or calculated using the Cockcroft-Gault formula).
- •Male or female, age between 18 and 75 years.
- •Written informed consent must be obtained from the subject or their legal representative.
- •Participants regardless of sex must agree to use effective contraception during the study period and for 3 months following treatment completion.
- •Willingness and ability to comply with visit schedules, treatment plans, and laboratory assessments.
排除标准
- •Histopathologically confirmed small cell carcinoma components.
- •Presence of multiple pulmonary nodules.
- •Incomplete resections (R1/R2) or resections via bilateral lobectomy, pneumonectomy, or wedge resection.
- •A history of any systemic anti-tumor treatment, including but not limited to surgery, neoadjuvant chemotherapy, radiotherapy, targeted therapy, or immunotherapy.
- •Significant allergies to any targeted drugs, immunotherapies, or chemotherapy agents used in the study.
- •Previous use of any traditional Chinese medicine with anti-tumor properties, or use of such medicine within 2 weeks prior to surgery.
- •History of other malignancies within the past 5 years, with the exception of the following:
- •Other malignancies fully cured by surgery with a disease-free survival of more than 10 years
- •Curable basal cell carcinoma of the skin
- •Bladder carcinoma in situ
- •Cervical carcinoma in situ
- •History of interstitial lung disease, drug-induced interstitial lung disease, radiation-induced pneumonia requiring steroid treatment, or any evidence of clinically active interstitial lung disease.
- •Active hepatitis B, defined as HBsAg positive with an HBV-DNA copy number exceeding the ULN established by the study center, accompanied by abnormal liver function, or requiring treatment as evaluated by the investigator.
- •Presence of any unstable systemic disease, including but not limited to active infection, uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the past 3 months, serious arrhythmias that requires medication, liver disease, kidney disease, or metabolic disorders.
- •Evidence of any other diseases, neurological or metabolic disorders, or physical exam or laboratory findings that may suggest contraindications for the investigational drug, or a high risk for treatment-related complications.
- •Any of the following cardiac conditions:
- •Resting ECG QT interval (QTc) > 470 msec.
- •Significant abnormalities in rhythm, conduction, or morphology on resting ECG, including complete left bundle branch block, third-degree atrioventricular block, or second-degree atrioventricular block
- •Factors increasing the risk of QTc prolongation or arrhythmic events, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, unexplained sudden death in a first-degree relative under the age of 40, or use of medications known to prolong QT interval.
- •Blood transfusion within 2 weeks prior to and during the surgery.
- •History of alcohol or drug abuse.
- •Pregnant or breastfeeding females.
- •Any other factors that the investigator deems may affect the progress of the study or compromise the trial data
研究组 & 干预措施
MRD-guided management
Patients who are MRD-positive after surgery in the MRD-guided management group receive adjuvant therapy. Patients who are MRD-negative in the MRD-guided management group are monitored through observation.
干预措施: Osimertinib (Drug)
MRD-guided management
Patients who are MRD-positive after surgery in the MRD-guided management group receive adjuvant therapy. Patients who are MRD-negative in the MRD-guided management group are monitored through observation.
干预措施: Alectinib (Drug)
MRD-guided management
Patients who are MRD-positive after surgery in the MRD-guided management group receive adjuvant therapy. Patients who are MRD-negative in the MRD-guided management group are monitored through observation.
干预措施: TORIPALIMAB INJECTION (JS001 ) combine with chemotherapy (Drug)
结局指标
主要结局
3-Year disease-free survival (DFS) Rate
时间窗: 3 years post randomization
The proportion of patients remain disease-free at the 3-year mark starting from the day of randomization
次要结局
- 5-Year disease-free survival (DFS) Rate(5 years post randomization)
- 5-Year overall survival (OS) rate(5 years post randomization)
- Disease-free survival (DFS)(Up to 8 years post randomization)
- Overall survival(Up to 8 years post randomization)
- Quality of Life (QoL) Assessed using the EORTC QLQ-C30 (Version 3.0)(Up to 8 years post randomization)
- Quality of Life (QoL) Assessed using the EORTC QLQ-LC13(Up to 8 years post randomization)
研究者
Xue-Ning Yang
Principal Investigator
Guangdong Association of Clinical Trials