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

NCT ID: NCT07293247

Last Updated: 2025-12-22

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 164 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-03-14
• Study Completion Date: 2032-03-01

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.

Detailed Description

PRIMARY OBJECTIVES:

I. To assess whether intensity-modulated post-operative radiation therapy (I²-PORT) improves disease-free survival (DFS) of patients with R0 resected ypN2 NSCLC compared to standard of care (SOC).

II. To assess whether I²-PORT does not unacceptably increase (by ≥ 6.5 percentage points) the rate of severe (grade ≥ 3 per Common Terminology Criteria for Adverse Events [CTCAE] version [v] 5) late cardiopulmonary toxicity compared to SOC.

SECONDARY OBJECTIVES:

I. 5-year DFS, 2- and 5-year overall survival (OS). II. Local versus (vs.) regional control, rate of distant metastases. III. Acute and late adverse events (AE) rates of specific cardiac, pulmonary, and other toxicities, per CTCAE version 5.0.

IV. Rates of non-mild, moderate, or severe-very severe symptoms per Patient Reported Outcomes - Common Terminology Criteria for Adverse Events (PRO-CTCAE), particularly terms related to cardiopulmonary toxicities, e.g., pain, shortness of breath, cough, wheezing, and heart palpitations.

V. Subset analyses by single vs. multi-station N2 and by adequacy of surgical nodal evaluation.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive SOC chemotherapy or immunotherapy on study. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) and/or magnetic resonance imaging (MRI), fludeoxyglucose-positron emission tomography (FDG-PET), and blood sample collection throughout the study.

ARM II: Patients undergo I²-PORT once daily (QD) Monday through Friday over 15-25 fractions over 5-6 weeks, starting 4-12 weeks after surgery. Radiation simulation should be performed within 21 days of starting I²-PORT. Starting 1-42 days after completion of I²-PORT, patients receive SOC chemotherapy or immunotherapy on the 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.

After completion of study treatment, patients are followed up every 3 months for 2 years, and then every 6 months for 3 years.

Conditions

Lung Non-Small Cell Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I (SOC chemotherapy/immunotherapy)

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.

Group Type: ACTIVE_COMPARATOR

Chemotherapy

Intervention Type: DRUG

Receive standard of care chemotherapy

Immunotherapy

Intervention Type: OTHER

Receive standard of care immunotherapy

Computed Tomography

Intervention Type: PROCEDURE

Undergo CT

Magnetic Resonance Imaging

Intervention Type: PROCEDURE

Undergo MRI

Fludeoxyglucose F-18

Intervention Type: OTHER

Undergo FDG PET scan

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo blood sample collection

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

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.

Group Type: EXPERIMENTAL

Chemotherapy

Intervention Type: DRUG

Receive standard of care chemotherapy

Immunotherapy

Intervention Type: OTHER

Receive standard of care immunotherapy

Intensity-Modulated Radiation Therapy

Intervention Type: RADIATION

Undergo I²-PORT

Computed Tomography

Intervention Type: PROCEDURE

Undergo CT

Magnetic Resonance Imaging

Intervention Type: PROCEDURE

Undergo MRI

Fludeoxyglucose F-18

Intervention Type: OTHER

Undergo FDG PET scan

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo blood sample collection

Interventions

Chemotherapy

Receive standard of care chemotherapy

Intervention Type: DRUG

Immunotherapy

Receive standard of care immunotherapy

Intervention Type: OTHER

Intensity-Modulated Radiation Therapy

Undergo I²-PORT

Intervention Type: RADIATION

Computed Tomography

Undergo CT

Intervention Type: PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

Intervention Type: PROCEDURE

Fludeoxyglucose F-18

Undergo FDG PET scan

Intervention Type: OTHER

Biospecimen Collection

Undergo blood sample collection

Intervention Type: PROCEDURE

Other Intervention Names

IMRT; CAT Scan; CT Scan; MRI; PET Scan

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Kozono, MD

Role: STUDY_CHAIR

Alliance for Clinical Trials in Oncology

Jeremy Brownstein, MD

Role: STUDY_CHAIR

Alliance for Clinical Trials in Oncology

Central Contacts

Amanda Clark

Role: CONTACT

Phone: 773-702-9171

Email: lungprotocols@alliancenctn.org

Other Identifiers

A082402

Identifier Type: -

Identifier Source: org_study_id