A Study of Targeted Post-Surgery Radiation Therapy for Non-Small Cell Lung Cancer With Remaining Lymph Node Cancer After Treatment

NCT07293247 | Not Yet Recruiting Phase 2

• 1 other identifier: A082402
• Study Type: interventional
• Target: 164
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Lung Non-Small Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• Disease-free survival (DFS)

  DFS will be analyzed using the Kaplan-Meier methodology and compared between Arm 2 and Arm 1 using a log-rank test stratified by randomization factors. The median DFS for each treatment group will be estimated, and its 80% and 90% confidence intervals will be calculated using the Kaplan-Meier estimator. Additionally, the 24-month DFS rate for each treatment arm, along with its confidence intervals, will be calculated.

  Time from the date of randomization to the date of earliest disease recurrence/progression or deaths of all causes, assessed up to 5 years

• Incidence of late grade ≥ 3 cardiopulmonary toxicities

  Will be assessed according to the Common Terminology Criteria for Adverse Events version 5.0. Will be estimated for each treatment group and the difference between the two treatment groups. The confidence intervals of the rate difference at 80% and 90% significance levels will be estimated using the Miettinen-Nurminen method.

  Between 3 and 24 months after protocol therapy

Secondary Outcomes (4)

• 5-year DFS

  Time from the date of randomization to the date of earliest disease recurrence/progression or deaths of all causes, assessed up to 5 years

• 2-year overall survival (OS)

  Time from the date of randomization to death from all causes, assessed up to 2 years

• 5-year OS

  Time from the date of randomization to death from all causes, assessed up to 5 years Symptomatic skeletal event free survival (SSE-FS)

• Patient-reported symptoms

  up to 5 years

Study Arms (2)

Arm I (SOC chemotherapy/immunotherapy)

ACTIVE COMPARATOR

Patients receive SOC chemotherapy or immunotherapy on study. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI, FDG-PET, and blood sample collection throughout the study.

Drug: Chemotherapy; Other: Immunotherapy; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Other: Fludeoxyglucose F-18; Procedure: Biospecimen Collection

Arm II (I²-PORT, SOC chemotherapy/immunotherapy)

EXPERIMENTAL

Patients undergo I²-PORT QD Monday through Friday over 15-25 fractions over 5-6 weeks. Starting 1-42 days after completion of I²-PORT, patients receive SOC chemotherapy or immunotherapy on study. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI, FDG-PET, and blood sample collection throughout the study.

Drug: Chemotherapy; Other: Immunotherapy; Radiation: Intensity-Modulated Radiation Therapy; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Other: Fludeoxyglucose F-18; Procedure: Biospecimen Collection

Interventions

Chemotherapy DRUG

Receive standard of care chemotherapy

Arm I (SOC chemotherapy/immunotherapy); Arm II (I²-PORT, SOC chemotherapy/immunotherapy)

Immunotherapy OTHER

Receive standard of care immunotherapy

Arm I (SOC chemotherapy/immunotherapy); Arm II (I²-PORT, SOC chemotherapy/immunotherapy)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT Scan, CT Scan

Arm I (SOC chemotherapy/immunotherapy); Arm II (I²-PORT, SOC chemotherapy/immunotherapy)

Intensity-Modulated Radiation Therapy RADIATION

Undergo I²-PORT

Also known as: IMRT

Arm II (I²-PORT, SOC chemotherapy/immunotherapy)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: MRI

Arm I (SOC chemotherapy/immunotherapy); Arm II (I²-PORT, SOC chemotherapy/immunotherapy)

Fludeoxyglucose F-18 OTHER

Undergo FDG PET scan

Also known as: PET Scan

Arm I (SOC chemotherapy/immunotherapy); Arm II (I²-PORT, SOC chemotherapy/immunotherapy)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Arm I (SOC chemotherapy/immunotherapy); Arm II (I²-PORT, SOC chemotherapy/immunotherapy)

Eligibility Criteria

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

* 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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Alliance for Clinical Trials in Oncology: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Drug Therapy; Immunotherapy; Radiotherapy, Intensity-Modulated; Magnetic Resonance Spectroscopy; Fluorodeoxyglucose F18

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Immunomodulation; Biological Therapy; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Deoxyglucose; Deoxy Sugars; Carbohydrates

Study Officials

• David Kozono, MD

  Alliance for Clinical Trials in Oncology

  STUDY CHAIR

• Jeremy Brownstein, MD

  Alliance for Clinical Trials in Oncology

  STUDY CHAIR

Central Study Contacts

Amanda Clark

CONTACT

773-702-9171; lungprotocols@alliancenctn.org

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: December 17, 2025
• First Posted: December 19, 2025
• Study Start: March 14, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): March 1, 2032
• Last Updated: December 22, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share