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Updated June 2026 · ClinicalTrials.gov

RECRUITINGPhase 3INTERVENTIONAL

Testing the Addition of High Dose, Targeted Radiation to the Usual Treatment for Locally-Advanced Inoperable Non-Small Cell 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

Testing the Addition of High Dose, Targeted Radiation to the Usual Treatment for Locally-Advanced Inoperable Non-Small Cell Lung Cancer (NCT05624996) is a Phase 3 interventional studying Locally Advanced Lung Non-Small Cell Carcinoma and Stage IIB Lung Cancer AJCC v8, sponsored by NRG Oncology. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

This phase III trial compares the effect of adding stereotactic body radiation therapy (SBRT) to the usual treatment (conventional image guided radiation therapy \[IGRT\] and chemotherapy followed by immunotherapy with durvalumab or targeted therapy with osimertinib) versus the usual treatment alone in treating patients with non-small cell lung cancer that has spread to nearby tissue or lymph nodes (locally advanced) and cannot be treated by surgery (inoperable). SBRT uses special equipment to position a patient and deliver radiation therapy to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. IGRT is a type of radiation therapy that creates a picture of the tumor to help guide the radiation beam during therapy, making it more accurate and causing less damage to healthy tissue. Usual chemotherapy used in this trial consists of combinations of the following drugs: cisplatin, carboplatin, paclitaxel, nab-paclitaxel, pemetrexed, and etoposide. Cisplatin and carboplatin are in a class of medications known as platinum-containing compounds. Cisplatin works by killing, stopping, or slowing the growth of tumor cells. Carboplatin works in a way similar to the anticancer drug cisplatin but may be better tolerated than cisplatin. Carboplatin works by killing, stopping, or slowing the growth of tumor cells as well. Paclitaxel is in a class of medications called antimicrotubule agents. It works by stopping the growth and spread of tumor cells. Nab-paclitaxel is an albumin-stabilized nanoparticle formulation of paclitaxel which may have fewer side effects and work better than other forms of paclitaxel. Pemetrexed is in a class of medications called antifolate antineoplastic agents. It works by blocking the action of a certain substance in the body that may help tumor cells multiply. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and deoxyribonucleic acid (DNA) repair and may kill tumor cells. Immunotherapy with durvalumab can induce changes in the body's immune system and can interfere with the ability of tumor cells to grow and spread. Osimertinib is in a class of medications called kinase inhibitors. It works by blocking the action of a protein called EGFR that signals cancer cells to multiply. This helps slow or stop the spread of tumor cells. Adding SBRT to the usual treatment of IGRT with chemotherapy and immunotherapy may be more effective at treating patients with locally-advanced non-small cell lung cancer than giving the usual treatment alone.

What Stage of Research Is This?

Phase 3 trials confirm efficacy and safety in large patient groups (often 300–3,000+) and form the evidence base for an FDA approval submission. For Locally Advanced Lung Non-Small Cell Carcinoma, Phase 3 studies typically randomize participants between the investigational treatment and either a placebo or current standard of care. A successful Phase 3 result is the threshold most treatments need to clear before regulatory approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

A target enrollment of 474 participants makes this a sizable late-stage trial. Studies in this range typically have enough power to detect clinically meaningful differences from a comparator and to characterize less-common side effects.

Who May Be Eligible (Plain English)

Who May Qualify: - 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 ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language
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

Treatments Being Tested

DRUG

Carboplatin

Given IV

DRUG

Cisplatin

Given IV

PROCEDURE

Computed Tomography

Undergo CT and/or PET/CT

BIOLOGICAL

Durvalumab

Given IV

DRUG

Etoposide

Given IV

RADIATION

Image Guided Radiation Therapy

Undergo IGRT

DRUG

Nab-paclitaxel

Given IV

DRUG

Osimertinib

Given PO

DRUG

Paclitaxel

Given IV

DRUG

Pemetrexed

Given IV

PROCEDURE

Positron Emission Tomography

Undergo PET/CT

OTHER

Questionnaire Administration

Ancillary studies

RADIATION

Stereotactic Body Radiation Therapy

Undergo SBRT

Locations (20)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
The Kirklin Clinic at Acton Road
Birmingham, Alabama, United States
Gulf Health Hospitals Inc/Infirmary Cancer Care - Malbis
Daphne, Alabama, United States
Thomas Hospital
Fairhope, Alabama, United States
Mobile Infirmary Medical Center
Mobile, Alabama, United States
Gulf Health Hospitals Inc/Infirmary Cancer Care - Saraland
Saraland, Alabama, United States
Kingman Regional Medical Center
Kingman, Arizona, United States
Cancer Center at Saint Joseph's
Phoenix, Arizona, United States
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, United States
Banner University Medical Center - Tucson
Tucson, Arizona, United States
University of Arizona Cancer Center-North Campus
Tucson, Arizona, United States
NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
Jonesboro, Arkansas, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
AIS Cancer Center at San Joaquin Community Hospital
Bakersfield, California, United States
Mills-Peninsula Medical Center
Burlingame, California, United States
Palo Alto Medical Foundation-Fremont
Fremont, California, United States
Los Angeles General Medical Center
Los Angeles, California, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
Fremont - Rideout Cancer Center
Marysville, California, United States
Memorial Medical Center
Modesto, California, United States

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT05624996), the sponsor (NRG Oncology), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT05624996 clinical trial studying?

This phase III trial compares the effect of adding stereotactic body radiation therapy (SBRT) to the usual treatment (conventional image guided radiation therapy \[IGRT\] and chemotherapy followed by immunotherapy with durvalumab or targeted therapy with osimertinib) versus the usual treatment alone in treating patients with non-small cell lung cancer that has spread to nearby tissue or lymph nodes (locally advanced) and cannot be treated by surgery (inoperable). SBRT uses special equipment to position a patient and deliver radiation therapy to tumors with high precision. This method may kill … The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT05624996?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT05624996?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT05624996. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT05624996. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-06-07 · Data from ClinicalTrials.gov.