A Phase 2 interventional study of Chemotherapy and Immunotherapy in Lung Non-Small Cell Carcinoma, sponsored by Alliance for Clinical Trials in Oncology. Recruiting at 111 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-02.
Sponsored by Alliance for Clinical Trials in Oncology · Phase 2, Interventional, and Treatment
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.
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.
IV. Rates of non-mild, moderate, or severe-very severe symptoms per Patient Reported Outcomes - Common Terminology Criteria for Adverse Events (PRO-CTCAE), particularly terms related to cardiopulmonary toxicities, e.g., pain, shortness of breath, cough, wheezing, and heart palpitations.
V. Subset analyses by single vs. multi-station N2 and by adequacy of surgical nodal evaluation.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive SOC chemotherapy or immunotherapy on study. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) and/or magnetic resonance imaging (MRI), fludeoxyglucose-positron emission tomography (FDG-PET), and blood sample collection throughout the study.
ARM II: Patients undergo I²-PORT once daily (QD) Monday through Friday over 15-25 fractions over 5-6 weeks, starting 4-12 weeks after surgery. Radiation simulation should be performed within 21 days of starting I²-PORT. Starting 1-42 days after completion of I²-PORT, patients receive SOC chemotherapy or immunotherapy on the 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.
After completion of study treatment, patients are followed up every 3 months for 2 years, and then every 6 months for 3 years.
6,488 studies on the registry are indexed under Carcinoma, Non-Small-Cell Lung; 1,632 are open to participants now.
This study's planned enrollment of 164 is above the median of 62 across 5,213 interventional studies indexed under Carcinoma, Non-Small-Cell Lung.
Browse Carcinoma, Non-Small-Cell Lung studies →Alliance for Clinical Trials in Oncology is the lead sponsor of 499 studies on the registry; 27 are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 6 (100%) have results posted.
Counted across the registry records on this site, refreshed daily.
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.
Drug: Chemotherapy · Other: Immunotherapy · Procedure: Computed Tomography · Procedure: Magnetic Resonance Imaging · Other: Fludeoxyglucose F-18 · Procedure: Biospecimen Collection
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.
Drug: Chemotherapy · Other: Immunotherapy · Radiation: Intensity-Modulated Radiation Therapy · Procedure: Computed Tomography · Procedure: Magnetic Resonance Imaging · Other: Fludeoxyglucose F-18 · Procedure: Biospecimen Collection
Receive standard of care chemotherapy
Receive standard of care immunotherapy
Undergo I²-PORT
Also known as: IMRT
Undergo CT
Also known as: CAT Scan, CT Scan
Undergo MRI
Also known as: MRI
Undergo FDG PET scan
Also known as: PET Scan
Undergo blood sample collection
Disease-free survival (DFS)
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.
Time frame: Time from the date of randomization to the date of earliest disease recurrence/progression or deaths of all causes, assessed up to 5 years
Incidence of late grade ≥ 3 cardiopulmonary toxicities
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.
Time frame: Between 3 and 24 months after protocol therapy
5-year DFS
DFS will be analyzed using the Kaplan-Meier methodology and compared between Arm 2 and Arm 1
Time frame: 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)
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. Multivariable Cox models will evaluate the treatment effect on survival time and its interaction with baseline covariates, including stage, pre-treatment, histology, and performance status.
Time frame: Time from the date of randomization to death from all causes, assessed up to 2 years
5-year OS
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. Multivariable Cox models will evaluate the treatment effect on survival time and its interaction with baseline covariates, including stage, pre-treatment, histology, and performance status.
Time frame: 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
Will be assessed using Patient Reported Outcomes - Common Terminology Criteria for Adverse Events and will be evaluated for between-arm differences in proportions of patients with a maximum post-baseline score greater than 0 using Fisher's exact or chi-square test.
Time frame: up to 5 years
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Plan to share: No
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From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Carcinoma, Non-Small-Cell Lung→
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