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A Study of Targeted Post-Surgery Radiation Therapy for Non-Small Cell Lung Cancer with Remaining Lymph Node Cancer After Treatment
Trial Status: active
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 that standard therapy alone in reducing the risk of cancer returning in who have undergone surgery for NSCLC.
Inclusion Criteria
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
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
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT07293247.
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 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.
After completion of study treatment, patients are followed up every 3 months for 2 years, and then every 6 months for 3 years.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationAlliance for Clinical Trials in Oncology
