Involved-Station, Intensity-Modulated Post-Operative Radiation Therapy (I²-PORT) for Resected Non-Small Cell Lung Cancer With Residual Mediastinal Adenopathy After Neoadjuvant Therapy (ypN2)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 164
- 试验地点
- 97
- 主要终点
- Disease-free survival (DFS)
研究概览
简要总结
This phase II trial compares the effect of intensity-modulated post-operative radiation therapy (I²-PORT) followed by standard of care therapy (chemotherapy or immunotherapy) to standard of care therapy alone in treating patients with non-small cell lung cancer (NSCLC) who have remaining lymph node cancer after surgery. Radiation therapy uses high-energy X-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Intensity-modulated radiation therapy is a type of 3-dimensional radiation therapy that uses computer-generated images to show the size and shape of the tumor. Thin beams of radiation of different intensities are aimed at the tumor from many angles. This type of radiation therapy reduces the damage to healthy tissue near the tumor. Chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Adding I²-PORT radiation therapy to standard therapy may be more effective than standard therapy alone in reducing the risk of cancer returning in those who have undergone surgery for NSCLC.
详细描述
PRIMARY OBJECTIVES:
I. To assess whether intensity-modulated post-operative radiation therapy (I²-PORT) improves disease-free survival (DFS) of patients with R0 resected ypN2 NSCLC compared to standard of care (SOC).
II. To assess whether I²-PORT does not unacceptably increase (by ≥ 6.5 percentage points) the rate of severe (grade ≥ 3 per Common Terminology Criteria for Adverse Events [CTCAE] version [v] 5) late cardiopulmonary toxicity compared to SOC.
SECONDARY OBJECTIVES:
I. 5-year DFS, 2- and 5-year overall survival (OS). II. Local versus (vs.) regional control, rate of distant metastases. III. Acute and late adverse events (AE) rates of specific cardiac, pulmonary, and other toxicities, per CTCAE version 5.0.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histopathologic diagnosis of NSCLC, may have mixed or multiple histologies but no small cell component
- •No known EGFR mutation or ALK rearrangement
- •No metastatic disease (M0) per most recent PET/CT and head CT/MRI imaging
- •No disease progression per CT chest (including upper abdomen as per standard practice) with intravenous (IV) contrast (unless IV contrast is contraindicated) or FDG-PET performed post-neoadjuvant therapy ≤ 90 days prior to registration, either before or after surgery
- •No metastatic disease (M0) per head CT/MRI imaging
- •Prior treatment with 2-4 cycles of neoadjuvant systemic therapy with any guideline (National Comprehensive Cancer Network [NCCN]) concordant regimen
- •Lobectomy or greater oncologic surgical resection within 8 weeks prior to registration
- •Complete (R0) resection showing ypN2 disease
- •No prior radiotherapy to the lungs or mediastinum
- •No treatment with a VEGF inhibitor ≤ 90 days prior to registration or plan to treat with adjuvant systemic therapy including a VEGF inhibitor
- •Age ≥ 18 years
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- •Absolute neutrophil count (ANC) ≥ 1,000/mm^3
- •Platelet count ≥ 50,000/mm^3
- •Calculated (Calc.) creatinine clearance ≥ 30 mL/min
- •Total bilirubin ≤ 3 x upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 5 x upper limit of normal (ULN)
- •Not pregnant, because this study involves radiation therapy, which has known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative urine or serum pregnancy test done ≤ 7 days prior to registration is required
- •Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
- •Cardiac function: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
- •No idiopathic pulmonary fibrosis requiring anti-fibrotic medication: Patients with idiopathic pulmonary fibrosis or inflammatory/interstitial lung disease compromising pulmonary function or requiring ongoing treatment with nintedanib, pirfenidone, or other anti-fibrotic drug are excluded
- •HIV-infected patients on effective anti-retroviral therapy with an undetectable viral load within 6 months are eligible for this trial
排除标准
- 未提供
研究组 & 干预措施
Arm II (I²-PORT, SOC chemotherapy/immunotherapy)
Patients undergo I²-PORT QD Monday through Friday over 15-25 fractions over 5-6 weeks. Starting 1-42 days after completion of I²-PORT, patients receive SOC chemotherapy or immunotherapy on study. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI, FDG-PET, and blood sample collection throughout the study.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm I (SOC chemotherapy/immunotherapy)
Patients receive SOC chemotherapy or immunotherapy on study. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI, FDG-PET, and blood sample collection throughout the study.
干预措施: Chemotherapy (Drug)
Arm I (SOC chemotherapy/immunotherapy)
Patients receive SOC chemotherapy or immunotherapy on study. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI, FDG-PET, and blood sample collection throughout the study.
干预措施: Immunotherapy (Other)
Arm I (SOC chemotherapy/immunotherapy)
Patients receive SOC chemotherapy or immunotherapy on study. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI, FDG-PET, and blood sample collection throughout the study.
干预措施: Biospecimen Collection (Procedure)
Arm II (I²-PORT, SOC chemotherapy/immunotherapy)
Patients undergo I²-PORT QD Monday through Friday over 15-25 fractions over 5-6 weeks. Starting 1-42 days after completion of I²-PORT, patients receive SOC chemotherapy or immunotherapy on study. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI, FDG-PET, and blood sample collection throughout the study.
干预措施: Biospecimen Collection (Procedure)
Arm I (SOC chemotherapy/immunotherapy)
Patients receive SOC chemotherapy or immunotherapy on study. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI, FDG-PET, and blood sample collection throughout the study.
干预措施: Computed Tomography (Procedure)
Arm I (SOC chemotherapy/immunotherapy)
Patients receive SOC chemotherapy or immunotherapy on study. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI, FDG-PET, and blood sample collection throughout the study.
干预措施: Fludeoxyglucose F-18 (Other)
Arm I (SOC chemotherapy/immunotherapy)
Patients receive SOC chemotherapy or immunotherapy on study. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI, FDG-PET, and blood sample collection throughout the study.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm II (I²-PORT, SOC chemotherapy/immunotherapy)
Patients undergo I²-PORT QD Monday through Friday over 15-25 fractions over 5-6 weeks. Starting 1-42 days after completion of I²-PORT, patients receive SOC chemotherapy or immunotherapy on study. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI, FDG-PET, and blood sample collection throughout the study.
干预措施: Fludeoxyglucose F-18 (Other)
Arm II (I²-PORT, SOC chemotherapy/immunotherapy)
Patients undergo I²-PORT QD Monday through Friday over 15-25 fractions over 5-6 weeks. Starting 1-42 days after completion of I²-PORT, patients receive SOC chemotherapy or immunotherapy on study. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI, FDG-PET, and blood sample collection throughout the study.
干预措施: Chemotherapy (Drug)
Arm II (I²-PORT, SOC chemotherapy/immunotherapy)
Patients undergo I²-PORT QD Monday through Friday over 15-25 fractions over 5-6 weeks. Starting 1-42 days after completion of I²-PORT, patients receive SOC chemotherapy or immunotherapy on study. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI, FDG-PET, and blood sample collection throughout the study.
干预措施: Intensity-Modulated Radiation Therapy (Radiation)
Arm II (I²-PORT, SOC chemotherapy/immunotherapy)
Patients undergo I²-PORT QD Monday through Friday over 15-25 fractions over 5-6 weeks. Starting 1-42 days after completion of I²-PORT, patients receive SOC chemotherapy or immunotherapy on study. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI, FDG-PET, and blood sample collection throughout the study.
干预措施: Immunotherapy (Other)
Arm II (I²-PORT, SOC chemotherapy/immunotherapy)
Patients undergo I²-PORT QD Monday through Friday over 15-25 fractions over 5-6 weeks. Starting 1-42 days after completion of I²-PORT, patients receive SOC chemotherapy or immunotherapy on study. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI, FDG-PET, and blood sample collection throughout the study.
干预措施: Computed Tomography (Procedure)
结局指标
主要结局
Disease-free survival (DFS)
时间窗: Time from the date of randomization to the date of earliest disease recurrence/progression or deaths of all causes, assessed up to 5 years
DFS will be analyzed using the Kaplan-Meier methodology and compared between Arm 2 and Arm 1 using a log-rank test stratified by randomization factors. The median DFS for each treatment group will be estimated, and its 80% and 90% confidence intervals will be calculated using the Kaplan-Meier estimator. Additionally, the 24-month DFS rate for each treatment arm, along with its confidence intervals, will be calculated.
Incidence of late grade ≥ 3 cardiopulmonary toxicities
时间窗: Between 3 and 24 months after protocol therapy
Will be assessed according to the Common Terminology Criteria for Adverse Events version 5.0. Will be estimated for each treatment group and the difference between the two treatment groups. The confidence intervals of the rate difference at 80% and 90% significance levels will be estimated using the Miettinen-Nurminen method.
次要结局
- 5-year DFS(Time from the date of randomization to the date of earliest disease recurrence/progression or deaths of all causes, assessed up to 5 years)
- 2-year overall survival (OS)(Time from the date of randomization to death from all causes, assessed up to 2 years)
- 5-year OS(Time from the date of randomization to death from all causes, assessed up to 5 years Symptomatic skeletal event free survival (SSE-FS))
- Patient-reported symptoms(up to 5 years)