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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

RecruitingPhase 2

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)

Who can join

Ages 18 and older · All sexes

Full eligibility 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

About the study

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.

What is being tested

Sponsor: Alliance for Clinical Trials in Oncology · Participants: 164 · Started: Oct 14, 2026

Contact the study team

Official record on ClinicalTrials.gov — NCT07293247

Locations in the U.S.

ArkansasNEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro, Jonesboro
CaliforniaUSC / Norris Comprehensive Cancer Center, Los Angeles
IllinoisIllinois CancerCare-Bloomington, Bloomington
OSF Saint Joseph Medical Center, Bloomington
Illinois CancerCare-Canton, Canton
Illinois CancerCare-Carthage, Carthage
Rush MD Anderson Cancer Center, Chicago
Cancer Care Specialists of Illinois - Decatur, Decatur
Decatur Memorial Hospital, Decatur
Illinois CancerCare-Eureka, Eureka
Illinois CancerCare-Galesburg, Galesburg
Illinois CancerCare-Kewanee Clinic, Kewanee
Illinois CancerCare-Macomb, Macomb
Cancer Care Center of O'Fallon, O'Fallon
HSHS Saint Elizabeth's Hospital, O'Fallon
Illinois CancerCare-Ottawa Clinic, Ottawa
Illinois CancerCare-Pekin, Pekin
OSF Saint Francis Radiation Oncology at Pekin, Pekin
Illinois CancerCare-Peoria, Peoria
OSF Saint Francis Medical Center, Peoria
OSF Saint Francis Radiation Oncology at Peoria Cancer Center, Peoria
Illinois CancerCare-Peru, Peru
Illinois CancerCare-Princeton, Princeton
Illinois CancerCare - Washington, Washington
MaineMaineHealth Coastal Cancer Treatment Center, Bath
MaineHealth Cancer Care and IV Therapy - Brunswick, Brunswick
MaineHealth Maine Medical Center - Portland, Portland
MaineHealth Cancer Care Center of York County, Sanford
MaineHealth Maine Medical Center- Scarborough, Scarborough
MaineHealth Cancer Care and IV Therapy - South Portland, South Portland
MichiganTrinity Health Saint Joseph Mercy Hospital Ann Arbor, Ann Arbor
Trinity Health IHA Medical Group Hematology Oncology - Brighton, Brighton
Trinity Health Medical Center - Brighton, Brighton
Trinity Health IHA Medical Group Hematology Oncology - Canton, Canton
Trinity Health Medical Center - Canton, Canton
Chelsea Hospital, Chelsea
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital, Chelsea
Trinity Health Saint Mary Mercy Livonia Hospital, Livonia
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus, Ypsilanti
MinnesotaSanford Joe Lueken Cancer Center, Bemidji
Essentia Health Saint Joseph's Medical Center, Brainerd
Essentia Health - Deer River Clinic, Deer River
Essentia Health Cancer Center, Duluth
Essentia Health Saint Mary's Medical Center, Duluth
Miller-Dwan Hospital, Duluth
Essentia Health Hibbing Clinic, Hibbing
Essentia Health Sandstone, Sandstone
Essentia Health Virginia Clinic, Virginia
MississippiBaptist Memorial Hospital and Cancer Center-Desoto, Southhaven
MissouriSaint Francis Medical Center, Cape Girardeau
New JerseyMemorial Sloan Kettering Basking Ridge, Basking Ridge
Memorial Sloan Kettering Monmouth, Middletown
Memorial Sloan Kettering Bergen, Montvale
New YorkMemorial Sloan Kettering Commack, Commack
Memorial Sloan Kettering Westchester, Harrison
Memorial Sloan Kettering Cancer Center, New York
New York Proton Center, New York
Upstate Cancer Center Radiation Oncology at Oswego, Oswego
Upstate Cancer Center at Oswego, Oswego
State University of New York Upstate Medical University, Syracuse
Upstate Cancer Center at Hill Radiation Oncology, Syracuse
Montefiore Medical Center - Moses Campus, The Bronx
Montefiore Medical Center-Einstein Campus, The Bronx
Memorial Sloan Kettering Nassau, Uniondale
Upstate Cancer Center at Verona, Verona
North CarolinaUNC Lineberger Comprehensive Cancer Center, Chapel Hill
North DakotaSanford Bismarck Medical Center, Bismarck
Sanford Broadway Medical Center, Fargo
Sanford Roger Maris Cancer Center, Fargo
OhioOhio State University Comprehensive Cancer Center, Columbus
PennsylvaniaUPMC-Heritage Valley Health System Beaver, Beaver
Carlisle Regional Cancer Center, Carlisle
UPMC Hillman Cancer Center Erie, Erie
UPMC Cancer Center at UPMC Horizon, Farrell
UPMC Cancer Centers - Arnold Palmer Pavilion, Greensburg
UPMC Pinnacle Cancer Center/Community Osteopathic Campus, Harrisburg
IRMC Cancer Center, Indiana
UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion, Mechanicsburg
Arnold Palmer Cancer Center Medical Oncology Norwin, N. Huntingdon
UPMC Hillman Cancer Center - New Castle, New Castle
UPMC Hillman Cancer Center, Pittsburgh
UPMC-Passavant Hospital, Pittsburgh
UPMC-Saint Clair Hospital Cancer Center, Pittsburgh
UPMC-Saint Margaret, Pittsburgh
UPMC-Shadyside Hospital, Pittsburgh
UPMC Cancer Center at UPMC Northwest, Seneca
UPMC Cancer Center-Washington, Washington
UPMC Washington Hospital Radiation Oncology, Washington
South DakotaSanford Cancer Center Oncology Clinic, Sioux Falls
Sanford USD Medical Center - Sioux Falls, Sioux Falls
TennesseeBaptist Memorial Hospital and Cancer Center-Collierville, Collierville
Baptist Memorial Hospital and Cancer Center-Memphis, Memphis
WisconsinDuluth Clinic Ashland, Ashland
Northwest Wisconsin Cancer Center, Ashland
Essentia Health-Hayward Clinic, Hayward
Essentia Health-Spooner Clinic, Spooner
Essentia Health Saint Mary's Hospital - Superior, Superior

Conditions

From ClinicalTrials.gov, data retrieved Sep 30, 2026. Each study sets its own eligibility; the study team decides who can join.