GCC 2545- Improving Post-Radiotherapy Respiratory Function Through Sparing Serial and Parallel Components in the Lung (INSPIRE)

Decreased respiratory function is a common side effect experienced by non-small cell lung cancer (NSCLC) patients who receive radiation therapy. In current clinical practice when treating cancerous lesions in the lung, it is not standard to explicitly try and avoid excessive radiation dose and therefore radiation injury to smaller airways. However, because of this patients may obtain damage to an airway segment can cause downstream regions in the lung to lose their "supply line" and, therefore, cause patients to lose the ability to exchange oxygen with the blood. The purpose of this clinical trial is to systematically compare post-treatment lung function of those who receive regular clinical radiation therapy (standard of care [SoC]) versus those who receive the airway-sparing radiation therapy regimen. The investigators hope to show that, by preserving airways and connected lung regions, participants will be able to retain a larger amount of their lung function, which will have a direct, positive impact on their post-treatment quality of life.

Study Overview

• Status: Not yet recruiting
• Conditions: Radiation; Lung Cancer (NSCLC)
• Intervention / Treatment: Radiation: SOC Radiation Treatment Planning; Radiation: INSPIRE Radiation Treatment Planning

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Amit Sawant, PhD; Phone Number: 410-328-6080; Email: asawant@som.umaryland.edu
• Study Contact Backup: Name: Caitlin Eggleston, MPH; Phone Number: 410-369-5351; Email: caitlineggleston@umm.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Greenebaum Cancer Center
      • Contact: Caitlin Eggleston, MPH; Phone Number: 410-369-5351; Email: caitlineggleston@umm.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Step 1- Inclusion Criteria

  1. Adult (≥18 years) patients (both sexes) with histologically diagnosed Stage III NSCLC per AJCC ver 9
  2. Patients to be treated with definitive external beam photon radiotherapy with or without systemic therapy (e.g., chemothrapy, immunotherapy).
  3. No restrictions on number radiotherapy fractions, or location/number of lesions
  4. ECOG performance status ≤ 3
  5. Ability to hold breath for ≥ 15 seconds
  6. Patient has signed informed consent document and agreed to study procedures

Step 2- Inclusion Criteria 1. Patient has completed 4DCT and BHCT with subsequent plans created and Radiation Oncologist has determined that patient would benefit from INSPIRE RT.

Exclusion Criteria:

• Step 1- Exclusion Criteria

  1. Prior lung cancer-directed radiotherapy
  2. Recent (< 12 mo) or planned lung surgery (which would confound pre- and post-RT lung function measures)
  3. Patients with metal implants or metal stents in the thoracic region
  4. Known severe chronic obstructive pulmonary disease or interstitial lung disease
  5. Women who are pregnant or trying to get pregnant

Step 2- Exclusion Criteria

1. Patient found to not benefit from INSPIRE RT after comparison of treatment plans.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1- SOC Radiation Plan; Standard RT Plan Creation	Radiation: SOC Radiation Treatment Planning; Two treatment plans will be created for each patient - an SOC RT plan and an INSPIRE RT plan. Both plans will fulfill clinical dosimetric objectives for tumor target and OARs, and will need to be reviewed and approved by the Radiation Oncologist. The trial will allow intensity modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT). Both techniques have been validated for INSPIRE RT previously. Both plans meet clinical dosimetric objectives. The INSPIRE plan achieves the additional goal of sparing functional units by better modulating the low dose and the intermediate dose compared to the SOC plan
Experimental: Arm 2- INSPIRE Radiation Plan; INSPIRE plan achieves the additional goal of sparing functional units by better modulating the low dose and the intermediate dose compared to the SOC plan.	Radiation: INSPIRE Radiation Treatment Planning; Two treatment plans will be created for each patient - an SOC RT plan and an INSPIRE RT plan. Both plans will fulfill clinical dosimetric objectives for tumor target and OARs, and will need to be reviewed and approved by the Radiation Oncologist. The trial will allow intensity modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT). Both techniques have been validated for INSPIRE RT previously. Both plans meet clinical dosimetric objectives. The INSPIRE plan achieves the additional goal of sparing functional units by better modulating the low dose and the intermediate dose compared to the SOC plan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of Post-Radiation retention of ventilation at 12 months through imaging.	The central objective of this trial is to determine if dose-sparing of airways and connected high-functioning sub-lobar lung volumes leads to superior preservation of post-RT ventilation compared to that achieved through SOC RT	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with Grade 2 or higher toxicities defined by Common Terminology Criteria for Adverse Events (CTCAE) v5	Local-regional control, radiographically-assessed change in radiation pneumonitis/lung fibrosis, Grade ≥ 2 toxicity per CTCAE definition.	12 months

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Investigators: Principal Investigator: Amit Sawant, PhD, University of Maryland, Baltimore

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2030

Study Registration Dates

• First Submitted: June 23, 2026
• First Submitted That Met QC Criteria: June 29, 2026
• First Posted (Actual): July 1, 2026

Study Record Updates

• Last Update Posted (Actual): July 1, 2026
• Last Update Submitted That Met QC Criteria: June 29, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: HP-00114566

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No