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

NCT07293247 | Recruiting Phase 2

• 2 other identifiers: A082402NCI-2025-06781
• Study Type: interventional
• Target: 164
• Locations: 1 country
• Sites: 111

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

Study Sites (111)

NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro

Jonesboro, Arkansas, 72401, United States

RECRUITING

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

RECRUITING

AdventHealth Parker

Parker, Colorado, 80138, United States

RECRUITING

OSF Saint Joseph Medical Center

Bloomington, Illinois, 61701, United States

RECRUITING

Illinois CancerCare-Bloomington

Bloomington, Illinois, 61704, United States

RECRUITING

Illinois CancerCare-Canton

Canton, Illinois, 61520, United States

RECRUITING

Illinois CancerCare-Carthage

Carthage, Illinois, 62321, United States

RECRUITING

Rush MD Anderson Cancer Center

Chicago, Illinois, 60612, United States

RECRUITING

Cancer Care Specialists of Illinois - Decatur

Decatur, Illinois, 62526, United States

RECRUITING

Decatur Memorial Hospital

Decatur, Illinois, 62526, United States

RECRUITING

Illinois CancerCare-Eureka

Eureka, Illinois, 61530, United States

RECRUITING

Illinois CancerCare-Galesburg

Galesburg, Illinois, 61401, United States

RECRUITING

Illinois CancerCare-Kewanee Clinic

Kewanee, Illinois, 61443, United States

RECRUITING

Illinois CancerCare-Macomb

Macomb, Illinois, 61455, United States

RECRUITING

Cancer Care Center of O'Fallon

O'Fallon, Illinois, 62269, United States

RECRUITING

HSHS Saint Elizabeth's Hospital

O'Fallon, Illinois, 62269, United States

RECRUITING

Illinois CancerCare-Ottawa Clinic

Ottawa, Illinois, 61350, United States

RECRUITING

Illinois CancerCare-Pekin

Pekin, Illinois, 61554, United States

RECRUITING

OSF Saint Francis Radiation Oncology at Pekin

Pekin, Illinois, 61554, United States

RECRUITING

Illinois CancerCare-Peoria

Peoria, Illinois, 61615, United States

RECRUITING

OSF Saint Francis Radiation Oncology at Peoria Cancer Center

Peoria, Illinois, 61615, United States

RECRUITING

OSF Saint Francis Medical Center

Peoria, Illinois, 61637, United States

RECRUITING

Illinois CancerCare-Peru

Peru, Illinois, 61354, United States

RECRUITING

Illinois CancerCare-Princeton

Princeton, Illinois, 61356, United States

RECRUITING

Illinois CancerCare - Washington

Washington, Illinois, 61571, United States

RECRUITING

Ascension Via Christi Hospitals Wichita

Wichita, Kansas, 67214, United States

RECRUITING

MaineHealth Coastal Cancer Treatment Center

Bath, Maine, 04530, United States

RECRUITING

MaineHealth Cancer Care and IV Therapy - Brunswick

Brunswick, Maine, 04011, United States

RECRUITING

MaineHealth Maine Medical Center - Portland

Portland, Maine, 04102, United States

RECRUITING

MaineHealth Cancer Care Center of York County

Sanford, Maine, 04073, United States

RECRUITING

MaineHealth Maine Medical Center- Scarborough

Scarborough, Maine, 04074, United States

RECRUITING

MaineHealth Cancer Care and IV Therapy - South Portland

South Portland, Maine, 04106, United States

RECRUITING

Trinity Health Saint Joseph Mercy Hospital Ann Arbor

Ann Arbor, Michigan, 48106, United States

RECRUITING

Trinity Health IHA Medical Group Hematology Oncology - Brighton

Brighton, Michigan, 48114, United States

RECRUITING

Trinity Health Medical Center - Brighton

Brighton, Michigan, 48114, United States

RECRUITING

Trinity Health IHA Medical Group Hematology Oncology - Canton

Canton, Michigan, 48188, United States

RECRUITING

Trinity Health Medical Center - Canton

Canton, Michigan, 48188, United States

RECRUITING

Chelsea Hospital

Chelsea, Michigan, 48118, United States

RECRUITING

Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital

Chelsea, Michigan, 48118, United States

RECRUITING

Trinity Health Saint Mary Mercy Livonia Hospital

Livonia, Michigan, 48154, United States

RECRUITING

Munson Medical Center

Traverse City, Michigan, 49684, United States

RECRUITING

Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus

Ypsilanti, Michigan, 48197, United States

RECRUITING

Sanford Joe Lueken Cancer Center

Bemidji, Minnesota, 56601, United States

RECRUITING

Essentia Health Saint Joseph's Medical Center

Brainerd, Minnesota, 56401, United States

RECRUITING

Essentia Health - Deer River Clinic

Deer River, Minnesota, 56636, United States

RECRUITING

Essentia Health Cancer Center

Duluth, Minnesota, 55805, United States

RECRUITING

Essentia Health Saint Mary's Medical Center

Duluth, Minnesota, 55805, United States

RECRUITING

Miller-Dwan Hospital

Duluth, Minnesota, 55805, United States

RECRUITING

Essentia Health Hibbing Clinic

Hibbing, Minnesota, 55746, United States

RECRUITING

Essentia Health Sandstone

Sandstone, Minnesota, 55072, United States

RECRUITING

Essentia Health Virginia Clinic

Virginia, Minnesota, 55792, United States

RECRUITING

Baptist Memorial Hospital and Cancer Center-Desoto

Southhaven, Mississippi, 38671, United States

RECRUITING

Saint Francis Medical Center

Cape Girardeau, Missouri, 63703, United States

RECRUITING

Parkland Health Center - Farmington

Farmington, Missouri, 63640, United States

RECRUITING

Sainte Genevieve County Memorial Hospital

Sainte Genevieve, Missouri, 63670, United States

RECRUITING

Missouri Baptist Medical Center

St Louis, Missouri, 63131, United States

RECRUITING

Missouri Baptist Sullivan Hospital

Sullivan, Missouri, 63080, United States

RECRUITING

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

RECRUITING

New York Proton Center

New York, New York, 10035, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Upstate Cancer Center at Oswego

Oswego, New York, 13126, United States

RECRUITING

Upstate Cancer Center Radiation Oncology at Oswego

Oswego, New York, 13126, United States

RECRUITING

State University of New York Upstate Medical University

Syracuse, New York, 13210, United States

RECRUITING

Upstate Cancer Center at Hill Radiation Oncology

Syracuse, New York, 13210, United States

RECRUITING

Montefiore Medical Center-Einstein Campus

The Bronx, New York, 10461, United States

RECRUITING

Montefiore Medical Center - Moses Campus

The Bronx, New York, 10467, United States

RECRUITING

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

RECRUITING

Upstate Cancer Center at Verona

Verona, New York, 13478, United States

RECRUITING

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Sanford Bismarck Medical Center

Bismarck, North Dakota, 58501, United States

RECRUITING

Sanford Broadway Medical Center

Fargo, North Dakota, 58122, United States

RECRUITING

Sanford Roger Maris Cancer Center

Fargo, North Dakota, 58122, United States

RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

Clackamas Radiation Oncology Center

Clackamas, Oregon, 97015, United States

RECRUITING

Providence Newberg Medical Center

Newberg, Oregon, 97132, United States

RECRUITING

Providence Willamette Falls Medical Center

Oregon City, Oregon, 97045, United States

RECRUITING

Providence Portland Medical Center

Portland, Oregon, 97213, United States

RECRUITING

Providence Saint Vincent Medical Center

Portland, Oregon, 97225, United States

RECRUITING

UPMC-Heritage Valley Health System Beaver

Beaver, Pennsylvania, 15009, United States

RECRUITING

Carlisle Regional Cancer Center

Carlisle, Pennsylvania, 17015, United States

RECRUITING

UPMC Hillman Cancer Center Erie

Erie, Pennsylvania, 16505, United States

RECRUITING

UPMC Cancer Center at UPMC Horizon

Farrell, Pennsylvania, 16121, United States

RECRUITING

UPMC Cancer Centers - Arnold Palmer Pavilion

Greensburg, Pennsylvania, 15601, United States

RECRUITING

UPMC Pinnacle Cancer Center/Community Osteopathic Campus

Harrisburg, Pennsylvania, 17109, United States

RECRUITING

IRMC Cancer Center

Indiana, Pennsylvania, 15701, United States

RECRUITING

UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion

Mechanicsburg, Pennsylvania, 17050, United States

RECRUITING

UPMC Cancer Center - Monroeville

Monroeville, Pennsylvania, 15146, United States

RECRUITING

UPMC Hillman Cancer Center - Monroeville

Monroeville, Pennsylvania, 15146, United States

RECRUITING

Arnold Palmer Cancer Center Medical Oncology Norwin

N. Huntingdon, Pennsylvania, 15642, United States

RECRUITING

UPMC Hillman Cancer Center - New Castle

New Castle, Pennsylvania, 16105, United States

RECRUITING

UPMC-Saint Margaret

Pittsburgh, Pennsylvania, 15215, United States

RECRUITING

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

UPMC-Shadyside Hospital

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

UPMC-Passavant Hospital

Pittsburgh, Pennsylvania, 15237, United States

RECRUITING

UPMC-Saint Clair Hospital Cancer Center

Pittsburgh, Pennsylvania, 15243, United States

RECRUITING

UPMC Cancer Center at UPMC Northwest

Seneca, Pennsylvania, 16346, United States

RECRUITING

UPMC Cancer Center-Washington

Washington, Pennsylvania, 15301, United States

RECRUITING

UPMC Washington Hospital Radiation Oncology

Washington, Pennsylvania, 15301, United States

RECRUITING

Sanford Cancer Center Oncology Clinic

Sioux Falls, South Dakota, 57104, United States

RECRUITING

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, 57117-5134, United States

RECRUITING

Baptist Memorial Hospital and Cancer Center-Collierville

Collierville, Tennessee, 38017, United States

RECRUITING

Baptist Memorial Hospital and Cancer Center-Memphis

Memphis, Tennessee, 38120, United States

RECRUITING

Duluth Clinic Ashland

Ashland, Wisconsin, 54806, United States

RECRUITING

Northwest Wisconsin Cancer Center

Ashland, Wisconsin, 54806, United States

RECRUITING

Essentia Health-Hayward Clinic

Hayward, Wisconsin, 54843, United States

RECRUITING

Essentia Health-Spooner Clinic

Spooner, Wisconsin, 54801, United States

RECRUITING

Essentia Health Saint Mary's Hospital - Superior

Superior, Wisconsin, 54880, United States

RECRUITING

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 (Estimated): October 14, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): March 1, 2032
• Last Updated: October 2, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (111)