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

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

Phase 3 Interventional NRG Oncology · NCT05624996

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
Enrollment474 (estimated)
Ages18 Years and up
SexAll
SponsorNRG Oncology Academic / other
Drugs / interventionschemotherapy, immunotherapy, radiation, durvalumab, osimertinib
Locations471 sites (Birmingham, Alabama and 470 other locations)
Trial IDNCT05624996 on ClinicalTrials.gov

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.

Who should consider this trial

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

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

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

Eligibility criteria

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 this trial is running

Birmingham, Alabama and 470 other locations

+421 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Locally Advanced Lung Non-Small Cell CarcinomaStage IIB Lung Cancer AJCC v8Stage III Lung Cancer AJCC v8
Last reviewed 2026-06-13 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.