Clinical trial Recruiting at 446 sites Phase 3 Interventional Ages 18 and up

Adding high dose targeted radiation to usual treatment for advanced lung cancer

Official title: Phase III Prospective Randomized Trial of Primary Lung Tumor Stereotactic Body Radiation Therapy Followed by Concurrent Mediastinal Chemoradiation for Locally-Advanced Non-Small Cell Lung Cancer

Run by NRG Oncology · NCT05624996 · Data updated 2026-11-12

This study is testing if adding a high dose of targeted radiation to the usual chemotherapy and immunotherapy can help people with advanced lung cancer live longer and feel better.

Quick facts

PhasePhase 3
Study typeInterventional
Ages18 Years and up
SexAll
Enrollment474 (estimated)
SponsorNRG Oncology
Academic / other
Drugs / interventionschemotherapy, immunotherapy, radiation, durvalumab, osimertinib
Locations477 sites (Birmingham, Alabama and 476 other locations)
StatusRecruiting
StartedJuly 12, 2023
Main results expectedOctober 15, 2031
Study endsOctober 15, 2036
Registry record updatedAugust 17, 2026
Trial IDNCT05624996 on ClinicalTrials.gov

Is this trial a fit for you?

Likely a good fit

Ideal candidates are patients with pathologically confirmed, inoperable stage IIB or III, node-positive non-small cell lung cancer.

Probably not a fit

Patients with operable lung cancer or those who have received extensive prior treatment may not benefit from this study.

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This phase III trial evaluates the effectiveness of adding stereotactic body radiation therapy (SBRT) to the standard treatment regimen of chemotherapy and immunotherapy for patients with locally advanced, inoperable non-small cell lung cancer (NSCLC). The study compares two treatment arms: one receiving conventional image-guided radiation therapy (IGRT) and the other receiving SBRT followed by conventional radiotherapy. The primary objectives include assessing overall survival and progression-free survival between the two groups, while secondary objectives focus on response rates, local control, and quality of life. The trial aims to determine if SBRT can improve outcomes with fewer doses and less damage to healthy tissue.

Why it matters

Potential benefit: If successful, this approach could lead to improved survival rates and quality of life for patients with advanced lung cancer.

How similar studies have gone: Other studies have shown promising results with SBRT in similar patient populations, indicating potential for success in this approach.

Who can join: the full rules

Show full inclusion / exclusion criteria
Inclusion Criteria:

* Pathologically (histologically or cytologically) proven diagnosis of non-operable stage IIB or III, node positive (American Joint Committee on Cancer \[AJCC\] eighth edition) non-small cell lung cancer (NSCLC) with known PD-L1 status prior to registration

  * Patients must have an identified primary tumor and at least one nodal metastasis (peribronchial/hilar/intrapulmonary, mediastinal/subcarinal, supraclavicular/scalene)
  * Up to 4 cycles of systemic therapy received prior to registration for the current study cancer is allowable; any prior chemotherapy for a different cancer is also permissible
  * Patients who refuse surgery, in addition to those who are technically unresectable or medically inoperable, are eligible.
  * Patients with separate tumor nodules in the same lobe of the primary tumor are eligible
* The patient must be deemed clinically appropriate for curative intent definitive combined modality therapy, based on the following staging assessments:

  * History/physical examination prior to registration;
  * Magnetic resonance imaging (MRI) scan of the brain (preferred) or CT scan of the brain (if available, contrast is preferred for all neuroimaging) prior to registration;
  * CT chest with IV contrast (if contrast is available and unless contraindicated, such as for abnormal kidney function) prior to registration. PET/CT may be used if the CT portion is of identical diagnostic quality as achieved in a stand-alone CT
* No evidence of distant metastases based on FDG PET/CT scan obtained within 60 days of registration
* Primary tumor =\< 7 cm
* Age \>= 18
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Hematologic function (e.g. platelets, leukocytes, hemoglobin) amenable, at the discretion of the treating physician, to allow for treatment with chemotherapy and concurrent radiation therapy
* Creatinine clearance \>= 25 mL/min by the Cockcroft-Gault (C-G) equation
* Subjects with non-malignant pleural effusion are eligible provided the effusion is not known or demonstrated to be an exudative effusion

  * If a pleural effusion is present, the following criteria must be met to exclude malignant involvement:

    * When pleural fluid is visible on both the CT scan and on a chest x-ray, a pleuracentesis is required to confirm that the pleural fluid is cytologically negative;
    * Effusions that are minimal (i.e., not visible on chest x-ray) that are too small to safely tap are eligible
* Medical history consistent with the patient being amenable, at the discretion of the treating physician, to allow for treating with consolidation immunotherapy. Patients with known EGFR/ALK/other driver mutation at the time of registration are eligible, and these patients can be treated with consolidation systemic therapy at the discretion of the treating physician
* 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
* Negative pregnancy test =\< 14 days prior to registration for participants of childbearing potential
* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information

Exclusion Criteria:

* Prior radiotherapy to the study cancer (local recurrence). Prior radiotherapy for a different cancer/condition to the region of the study cancer that would result in overlap of radiation therapy fields that is determined by the treating physician to impede the treatment of the study malignancy
* Patients without identifiable primary tumor and at least 1 pathologically enlarged lymph node are not eligible (T3-4N0 or T0N1-3 patients are not eligible). At least 1 radiographically-involved lymph node is required, but pathologic confirmation of involvement is not mandated
* Centrally located primary tumor \< 2 cm from involved nodal disease that would result in significant overlap of the primary SBRT and nodal radiation fields. This does not include proximity to involved segmental and subsegmental lymph nodes (levels 13 and 14) that would not result in overlap of dose to the proximal bronchial tree or esophagus. Centrally located is defined as within or touching the zone of the proximal bronchial tree, which is a volume 2 cm in all directions around the proximal bronchial tree (carina, right and left main bronchi, right and left upper lobe bronchi, intermedius bronchus, right middle lobe bronchus, lingular bronchus right and left lower lobe bronchi)
* Participants who are pregnant or unwilling to discontinue nursing
* Participants of childbearing potential (participants who may become pregnant or who may impregnate a partner) unwilling to use highly effective contraceptives during therapy and for the Food and Drug Administration (FDA)-labeled contraception timeframe required after the final dose of the selected systemic therapy regimen, because the treatment in this study may be significantly teratogenic

Where it's running

  • University of Alabama at Birmingham Cancer Center
    Birmingham, Alabama, United States
    Recruiting
  • The Kirklin Clinic at Acton Road
    Birmingham, Alabama, United States
    Recruiting
  • Gulf Health Hospitals Inc/Infirmary Cancer Care - Malbis
    Daphne, Alabama, United States
    Recruiting
  • Thomas Hospital
    Fairhope, Alabama, United States
    Recruiting
  • Mobile Infirmary Medical Center
    Mobile, Alabama, United States
    Recruiting
  • Gulf Health Hospitals Inc/Infirmary Cancer Care - Saraland
    Saraland, Alabama, United States
    Recruiting
Show 44 more locations
  • Kingman Regional Medical Center
    Kingman, Arizona, United States
    Recruiting
  • Cancer Center at Saint Joseph's
    Phoenix, Arizona, United States
    Recruiting
  • Mayo Clinic Hospital in Arizona
    Phoenix, Arizona, United States
    Recruiting
  • Banner University Medical Center - Tucson
    Tucson, Arizona, United States
    Recruiting
  • University of Arizona Cancer Center-North Campus
    Tucson, Arizona, United States
    Recruiting
  • NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
    Jonesboro, Arkansas, United States
    Recruiting
  • University of Arkansas for Medical Sciences
    Little Rock, Arkansas, United States
    Recruiting
  • AIS Cancer Center at San Joaquin Community Hospital
    Bakersfield, California, United States
    Recruiting
  • Mills-Peninsula Medical Center
    Burlingame, California, United States
    Recruiting
  • Palo Alto Medical Foundation-Fremont
    Fremont, California, United States
    Recruiting
  • Memorial Medical Center
    Modesto, California, United States
    Recruiting
  • Palo Alto Medical Foundation-Camino Division
    Mountain View, California, United States
    Recruiting
  • Palo Alto Medical Foundation Health Care
    Palo Alto, California, United States
    Recruiting
  • Sutter Cancer Centers Radiation Oncology Services-Roseville
    Roseville, California, United States
    Recruiting
  • Sutter Roseville Medical Center
    Roseville, California, United States
    Recruiting
  • Sutter Medical Center Sacramento
    Sacramento, California, United States
    Recruiting
  • California Pacific Medical Center-Pacific Campus
    San Francisco, California, United States
    Recruiting
  • Mills Health Center
    San Mateo, California, United States
    Recruiting
  • Sutter Pacific Medical Foundation
    Santa Rosa, California, United States
    Recruiting
  • Palo Alto Medical Foundation-Sunnyvale
    Sunnyvale, California, United States
    Recruiting
  • Sutter Solano Medical Center/Cancer Center
    Vallejo, California, United States
    Recruiting
  • UCHealth University of Colorado Hospital
    Aurora, Colorado, United States
    Recruiting
  • Rocky Mountain Cancer Centers-Penrose
    Colorado Springs, Colorado, United States
    Recruiting
  • UCHealth Memorial Hospital Central
    Colorado Springs, Colorado, United States
    Recruiting
  • Memorial Hospital North
    Colorado Springs, Colorado, United States
    Recruiting
  • UCHealth - Cherry Creek
    Denver, Colorado, United States
    Recruiting
  • Poudre Valley Hospital
    Fort Collins, Colorado, United States
    Recruiting
  • Cancer Care and Hematology-Fort Collins
    Fort Collins, Colorado, United States
    Recruiting
  • UCHealth Greeley Hospital
    Greeley, Colorado, United States
    Recruiting
  • UCHealth Highlands Ranch Hospital
    Highlands Ranch, Colorado, United States
    Recruiting
  • UCHealth Lone Tree Health Center
    Lone Tree, Colorado, United States
    Recruiting
  • Medical Center of the Rockies
    Loveland, Colorado, United States
    Recruiting
  • Beebe Medical Center
    Lewes, Delaware, United States
    Recruiting
  • Beebe South Coastal Health Campus
    Millville, Delaware, United States
    Recruiting
  • Helen F Graham Cancer Center
    Newark, Delaware, United States
    Recruiting
  • Medical Oncology Hematology Consultants PA
    Newark, Delaware, United States
    Recruiting
  • Christiana Care Health System-Christiana Hospital
    Newark, Delaware, United States
    Recruiting
  • Beebe Health Campus
    Rehoboth Beach, Delaware, United States
    Recruiting
  • Christiana Care Health System-Wilmington Hospital
    Wilmington, Delaware, United States
    Recruiting
  • Bay Pines VA Healthcare System
    Bay Pines, Florida, United States
    Recruiting
  • Morton Plant Hospital
    Clearwater, Florida, United States
    Recruiting
  • Halifax Health Cancer Center for Hope - Daytona Beach
    Daytona Beach, Florida, United States
    Recruiting
  • Memorial Regional Hospital/Joe DiMaggio Children's Hospital
    Hollywood, Florida, United States
    Recruiting
  • Mayo Clinic in Florida
    Jacksonville, Florida, United States
    Recruiting

+427 more sites. See ClinicalTrials.gov for the full list.

Study contacts

  • Principal investigator: Charles B Simone — NRG Oncology

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

How to take part

  1. Review the eligibility criteria above with your treating physician.
  2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
  3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.
Last reviewed 2026-11-14 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.