Testing Repeat Radiation Therapy for Recurrent Non-small Cell Lung Cancer

NCT07835789 | Not Yet Recruiting Phase 2

• 3 other identifiers: NRG-LU011NCI-2026-06282U10CA180868
• Study Type: interventional
• Target: 138
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase II trial compares repeat radiation therapy (RT) to standard drug treatment alone in treating patients with stage II-III non-small cell lung cancer (NSCLC) that has come back after initial radiation at or adjacent to the site of the original tumor (locally recurrent). Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Chemotherapy drugs used in standard drug treatment 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 drugs used in standard drug treatment may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Targeted therapy drugs used in standard treatment identify and attack specific tumor cells. This trial may help doctors determine whether repeat RT delays the cancer from growing or spreading by 6 months or more after initial radiation compared to standard drug treatment alone in patients with stage II-III locally recurrent NSCLC.

Conditions

Locally Recurrent Lung Non-Small Cell Carcinoma; Stage II Lung Cancer AJCC v8; Stage III Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  The primary analysis of PFS will be conducted in the intent-to-treat population, defined as all randomized patients. The distributions of PFS will be estimated by the Kaplan-Meier method. The primary comparison between arms will use a one-sided stratified log-rank test with the randomization stratification factors. A stratified Cox proportional hazards model will be used to estimate the hazard ratio and corresponding confidence interval. An unstratified log-rank test and unstratified Cox proportional hazards model will also be provided as sensitivity analyses. No post hoc modification or collapsing of stratification categories based on observed event counts will be performed. If the stratified Cox model is not estimable because of sparse data, the unstratified Cox model will be used to summarize the treatment hazard ratio and confidence interval, with the reason documented.

  From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first, assessed up to 5 years

Secondary Outcomes (4)

• Overall survival

  From randomization to death from any cause, assessed up to 5 years

• Incidence of clinician-scored treatment-related adverse events

  Up to 5 years

• Incidence of patient-reported adverse events

  Up to 5 years

• Site of first disease progression

  Up to 5 years

Other Outcomes (3)

• Clinical and dosimetric predictors of high-grade treatment-related toxicity

  Up to 5 years

• Radiotherapy modality toxicity and efficacy outcomes

  Up to 5 years

• Regional lung ventilation metrics

  Up to 5 years

Study Arms (2)

Arm 1 (SOC systemic therapy)

ACTIVE COMPARATOR

Patients receive SOC systemic therapy, which may include chemotherapy, immunotherapy, and/or targeted therapy on study. Patients also undergo PET/CT and MRI during screening, as well as chest CT and optional blood sample collection throughout the study.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Other: Immunotherapy; Procedure: Magnetic Resonance Imaging; Drug: Systemic Chemotherapy; Other: Targeted Therapy

Arm 2 (repeat RT, chemotherapy)

EXPERIMENTAL

Patients undergo RT for 20 treatment fractions over approximately 5 weeks or RT for 30 treatment fractions over approximately 6 weeks in the absence of disease progression or unacceptable toxicity. Patients receiving 6-week RT may also receive chemotherapy during RT per decision of patient and doctor decision. Patients also undergo PET/CT and MRI during screening, as well as chest CT and optional blood sample collection throughout the study.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Radiation: Radiation Therapy; Drug: Systemic Chemotherapy

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Arm 1 (SOC systemic therapy); Arm 2 (repeat RT, chemotherapy)

Immunotherapy OTHER

Given SOC immunotherapy

Also known as: Immunological, Immunological Therapy, Immunologically Directed Therapy

Arm 1 (SOC systemic therapy)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Arm 1 (SOC systemic therapy); Arm 2 (repeat RT, chemotherapy)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Arm 2 (repeat RT, chemotherapy)

Targeted Therapy OTHER

Given SOC targeted therapy

Also known as: Target/Mechanism, Targeted, Targeting Therapy

Arm 1 (SOC systemic therapy)

Computed Tomography PROCEDURE

Undergo PET/CT and/or chest CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Arm 1 (SOC systemic therapy); Arm 2 (repeat RT, chemotherapy)

Systemic Chemotherapy DRUG

Given SOC chemotherapy

Arm 1 (SOC systemic therapy); Arm 2 (repeat RT, chemotherapy)

Radiation Therapy RADIATION

Undergo repeat RT

Also known as: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Arm 2 (repeat RT, chemotherapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• History of stage II-III NSCLC treated with fractionated (≤ 4 Gy per fraction) curative-intent (total dose ≥ 45 Gy) thoracic radiotherapy, completed ≥ 12 months before study entry
• Participants must have recurrent/progressive disease in the lung and/or regional lymph nodes that is not suitable for treatment with stereotactic body radiation therapy (SBRT) and for which palliative thoracic radiotherapy is not required at the time of study entry
• Biopsy to confirm recurrent/progressive disease at some point after the previous course of thoracic radiotherapy and before entering this study is required
• A portion of the disease that would be treated with radiotherapy on Arm 2 of this protocol must fall within the 50% isodose cloud of the radiotherapy plan
• New systemic lung cancer therapy initiated within 12 weeks prior to study entry that is still ongoing is not permitted
• Participants must not have definitive clinical or radiographic evidence of distant metastatic NSCLC at present or in the past
• Age ≥ 18
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
• Not Pregnant and Not Nursing
• Negative urine or serum pregnancy test (in persons of childbearing potential) within 14 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal
• Prior thoracic radiotherapy for NSCLC must have been delivered as definitive treatment, as opposed to in the preoperative or postoperative setting. One prior radiotherapy course must meet the specifications, and the radiotherapy plan from that course must be available in Digital Imaging and Communications in Medicine (DICOM) format
• Patients who have received additional prior radiotherapy (i.e., more than one prior radiotherapy course) may be enrolled, provided that only one prior radiotherapy course is deemed to affect the risks associated with treatment with radiotherapy on this study. As examples, prior radiotherapy for an extrathoracic malignancy would likely not affect the risks associated with reirradiation on this study. Prior radiotherapy for breast cancer may be permissible, depending on the extent of lung irradiation. Similarly, prior SBRT for a peripheral lung tumor may be permissible
• No prior SBRT for a central lung tumor, hilar lymph node, or mediastinal lymph node
• Prior lobar and sublobar lung resections are allowed, but prior pneumonectomy is not allowed
• Prior chemotherapy, targeted therapy, and/or immunotherapy for lung cancer is allowed

Sponsors & Collaborators

• NRG Oncology: lead

MeSH Terms

Conditions

Lung Neoplasms

Interventions

Specimen Handling; Immunotherapy; Adjuvants, Immunologic; Magnetic Resonance Spectroscopy; Radiotherapy; Radiation; Neoadjuvant Therapy

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Factors; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Spectrum Analysis; Chemistry Techniques, Analytical; Physical Phenomena; Combined Modality Therapy

Study Officials

• Nitin Ohri

  NRG Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2026
• First Posted: September 23, 2026
• Study Start (Estimated): December 18, 2026
• Primary Completion (Estimated): September 30, 2029
• Study Completion (Estimated): September 30, 2034
• Last Updated: September 23, 2026

Record last verified: 2026-09