A Randomized Controlled Phase III Study of Adaptive Hypofractionated Radiotherapy Combined With Concurrent Chemotherapy and Consolidative Immunotherapy in Locally Advanced Non-Small Cell Lung Cancer Based on Dynamic Enhanced Magnetic Resonance Imaging
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 490
- 试验地点
- 1
- 主要终点
- treatment-related G2+ respiratory toxicity
研究概览
简要总结
This study is a randomized phase III trial that aiming to investigate the role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) guided hypofractionated radiotherapy (hypo-RT) in patients with locally advanced non-small cell lung cancer (LA-NSCLC) who are planned to receive hypo-RT combined with concurrent chemotherapy and consolidative immunotherapy. Patients will be randomized in a 1:1 ratio into two groups:
- The study group will undergo adaptive dose-painting hypo-RT based on DCE-MRI.
- The control group will undergo hypo-RT based on enhanced CT.
The treatment-related toxicity, local control and long-term survival will be evaluated compared between MRI-guided and CT-guided hypo-RT.
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
- •Male or female aged between 18 and 75 years old.
- •Patients must have histological or cytological confirmation of locally advanced, unresectable (stage III) non-small cell lung cancer (NSCLC).
- •No prior radiation therapy or surgery.
- •Expected life expectancy of at least 12 weeks.
- •World Health Organization (WHO) performance status score of 0 or
- •Able to undergo magnetic resonance imaging (MRI) examination.
- •Organ and bone marrow function meeting the following criteria: Forced expiratory volume in 1 second (FEV1) ≥ 800 ml; Absolute neutrophil count ≥ 1.5 × 10^9/L; Platelets ≥ 100 × 10^9/L; Hemoglobin ≥ 9.0 g/dL; Serum creatinine clearance rate calculated by the Cockcroft-Gault formula ≥ 50 mL/min (Cockcroft and Gault 1976); Serum bilirubin ≤ 1.5 times the upper limit of normal (ULN); Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 times ULN.
排除标准
- •Contraindications to MRI examination.
- •Concurrent participation in another clinical study, unless it is an observational (non-interventional) clinical study.
- •Histological type of mixed small cell and non-small cell lung cancer.
- •The presence of sensitive EGFR mutations or ALK rearrangements.
- •Major surgery performed within 4 weeks prior to entering the study (excluding vascular access).
- •History or occurrence of autoimmune disease within the past 2 years.
- •Active or history of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
- •History of primary immunodeficiency.
- •History of organ transplantation requiring immunosuppressive therapy.
- •Average QT interval (QTc) ≥ 470 ms calculated from 3 ECG cycles using Bazett's correction.
- •Uncontrolled comorbidities, including but not limited to persistent or active infection, symptomatic congestive heart failure, poorly controlled hypertension, unstable angina, arrhythmia, active peptic ulcer disease or gastritis, active bleeding disorder, human immunodeficiency virus (HIV), or psychiatric/social situations that would limit compliance with study requirements or impair the ability to provide written informed consent.
- •Active tuberculosis.
- •Receipt of a live attenuated vaccine within 30 days prior to the start of the study.
- •History of another primary malignancy within 5 years, excluding adequately treated basal or squamous cell skin cancer or in situ cervical cancer.
- •Pregnant or breastfeeding women; or males and females of reproductive potential not using effective contraception.
研究组 & 干预措施
MRI-based hypo-RT
Patients will receive split-course hypo-RT combined with concurrent chemotherapy and consolidative immunotherapy. The experimental arm will undergo adaptive dose-painting hypo-RT based on DCE-MRI.
干预措施: Concurrent chemotherapy (Drug)
MRI-based hypo-RT
Patients will receive split-course hypo-RT combined with concurrent chemotherapy and consolidative immunotherapy. The experimental arm will undergo adaptive dose-painting hypo-RT based on DCE-MRI.
干预措施: DCE-MRI based split-course hypo-RT (Radiation)
MRI-based hypo-RT
Patients will receive split-course hypo-RT combined with concurrent chemotherapy and consolidative immunotherapy. The experimental arm will undergo adaptive dose-painting hypo-RT based on DCE-MRI.
干预措施: Consolidative immunotherapy (Drug)
CT-based hypo-RT
Patients will receive split-course hypo-RT combined with concurrent chemotherapy and consolidative immunotherapy. The control arm will undergo hypo-RT based on CT.
干预措施: CT based split-course hypo-RT (Radiation)
CT-based hypo-RT
Patients will receive split-course hypo-RT combined with concurrent chemotherapy and consolidative immunotherapy. The control arm will undergo hypo-RT based on CT.
干预措施: Concurrent chemotherapy (Drug)
CT-based hypo-RT
Patients will receive split-course hypo-RT combined with concurrent chemotherapy and consolidative immunotherapy. The control arm will undergo hypo-RT based on CT.
干预措施: Consolidative immunotherapy (Drug)
结局指标
主要结局
treatment-related G2+ respiratory toxicity
时间窗: Recorded from the enrollment to 1 year after the completion of hypo-RT or 3 months after the completion of consolidative immunotherapy
the percentage of patients who developed G2+ respiratory toxicity, including pneumonitis and proximal bronchial tree toxicity
progression-free survival rate
时间窗: 2-year
次要结局
- local control rate(2-year)
- overall survival rate(2-year)
- patient reported outcome assessed by QLQ-C30(2 year)
- patient reported outcome(2 year)
研究者
Hui Liu
Professor
Sun Yat-sen University