A Study of Targeted Post-Surgery Radiation Therapy for Non-Small Cell Lung Cancer with Remaining Lymph Node Cancer After 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 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
- 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
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT07293247.
Locations matching your search criteria
United States
Arkansas
Jonesboro
Illinois
Decatur
O'Fallon
Michigan
Ann Arbor
Brighton
Canton
Chelsea
Livonia
Ypsilanti
Minnesota
Brainerd
Deer River
Duluth
Hibbing
Sandstone
Virginia
Mississippi
Southhaven
New York
Bronx
North Carolina
Chapel Hill
South Dakota
Sioux Falls
Tennessee
Collierville
Memphis
Wisconsin
Ashland
Hayward
Spooner
Superior
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 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
Principal InvestigatorDavid E. Kozono
- Primary IDA082402
- Secondary IDsNCI-2025-06781
- ClinicalTrials.gov IDNCT07293247