Hypofractionated Radiation Therapy to Improve Immunotherapy Response in Non-Small Cell Lung Cancer

March 12, 2025 updated by: West Virginia University

Use of Response-Adapted Hypofractionated Radiation Therapy to Potentiate the Systemic Immune Response to Checkpoint Inhibitors in Non-Small Cell Lung Cancer

This study includes the additional use of radiation therapy in combination immunotherapy in order to determine whether the radiation may improve the response of non-small cell lung cancer to immunotherapy and to monitor any side effects.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Preclinical data suggest that radiation therapy may be uniquely suited to combine with immune checkpoint inhibitors, since radiation can disrupt a tumor's physical barriers to T-cell infiltration and augment antigen presentation, thus serving as an "in situ personalized vaccine" to activate the immune system and potentially enhance the systemic response.

The rationale for this study is to determine the safety and efficacy of combined immune checkpoint inhibitors and radiation therapy in metastatic non-small cell lung cancer patients.

Study Type

Interventional

Enrollment (Actual)

35

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • WVU Cancer Institute - Mary Babb Randolph Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Stage IV metastatic Non Small Cell Lung Cancer
  • Measurable disease of at least 1.5 cm in greatest dimension at least 2 non-irradiated sites (except for lymph nodes, in which the short-axis dimension must be at least 1.5cm). There must be at least 1 visceral organ metastasis outside of the brain.
  • History of prior cytotoxic chemotherapy (with or without concomitant radiation therapy) with subsequent distant (metastatic) disease relapse, or progression of disease while on chemotherapy.
  • Participant must be planned to receive (or actively receiving) standard of care checkpoint inhibitor immune therapy. For those patients actively receiving checkpoint inhibitor immune therapy the duration of immune therapy at the time of enrollment must be 4 months or less.
  • Life expectancy greater than 3 months

Exclusion Criteria:

  • Active autoimmune disease, primary immunodeficiency syndrome, HIV/AIDS, or hepatitis B or C
  • Oral corticosteroid dependency
  • Uncontrolled or untreated active brain metastases/CNS disease
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Radiation Therapy + Immunotherapy
3-5 fraction course of radiation therapy to target lesion concurrent with an immuno-therapeutic agent
Radiation: Radiation
Radiation therapy will be administered in 3 or 5 fractions over 3-10 days, at a recommended dose of 8-15 Gy per fraction for 3 total fractions (total dose 24-45 Gy) or 6-10 Gy per fraction for 5 total fractions (total dose 30-50 Gy)
Other Names:
  • Hypofractionated Radiation
Drug: Immuno-Therapeutic Agent

Immune checkpoint inhibitors that are FDA approved for use in patients with metastatic NSCLC will be acceptable for use concurrently with radiotherapy in this trial. The choice of agents will be at the treating medical oncologist's discretion, and include:

  • Nivolumab 240mg or 3 mg/kg once every 2 weeks (14 day cycle)
  • Pembrolizumab 200mg or 2 mg/kg once every 3 weeks (21 day cycle)
  • Atezolizumab 1200 mg once every 3 weeks (21 day cycle)

These agents should be continued per standard of care until either disease progression or unacceptable toxicity.

Other Names:
  • Immunotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Best Overall Response
Time Frame: From the start of treatment until disease progression up to 2 years.
Time to Best Overall Response is measured in months from the start of treatment until the best response is achieved. Both RECIST v1.1 and irRC criteria will be used. RECIST Criteria: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): ≥30% decrease in the sum of the diameters of target lesions. Stable Disease (SD): Neither sufficient shrinkage for PR nor sufficient increase for PD. Progressive Disease (PD): ≥20% increase in the sum of the diameters of target lesions or appearance of new lesions. irRC Criteria: Complete Response (irCR): Disappearance of all lesions in two consecutive observations ≥4 weeks apart. Partial Response (irPR): ≥50% decrease in tumor burden compared with baseline in two observations ≥4 weeks apart. Stable Disease (irSD): Neither sufficient decrease for irPR nor sufficient increase for irPD. Progressive Disease (irPD): ≥25% increase in tumor burden compared with nadir in two consecutive observations ≥4 weeks apart.
From the start of treatment until disease progression up to 2 years.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: From the start of treatment until the date date of death, or the last follow up date on which the participant was reported alive, assessed up to 2 years
Amount of time from treatment until death, reported via follow up visit or phone call.
From the start of treatment until the date date of death, or the last follow up date on which the participant was reported alive, assessed up to 2 years
Time to Progression Free Survival
Time Frame: From the start of treatment until the date of documented progression or death assessed up to 2 years

The duration of time from start of treatment to time of progression or death, whichever occurs first. For those patients with a CR or PR, the reference for progressive disease is the smallest measurements recorded since the treatment started.

RECIST version 1.1 will be used to assess the local response of irradiated lesions only, taking as reference the baseline largest diameter:

Complete Response (CR) - Disappearance of the irradiated lesion Partial Response (PR) - > 30% decrease in the single largest diameter of the irradiated lesion Stable Disease (SD) - Neither sufficient decrease in diameter to qualify as PR nor sufficient increase in diameter to qualify as PD Progressive Disease (PD) - > 20% increase in the single largest diameter of the irradiated lesion. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm (0.5 cm).
From the start of treatment until the date of documented progression or death assessed up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

West Virginia University

Collaborators

West Virginia Clinical and Translational Science Institute

Investigators

  • Principal Investigator: Mohammad Shaikh, MD, West Virginia University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 23, 2017

Primary Completion (Actual)

June 30, 2022

Study Completion (Actual)

June 30, 2022

Study Registration Dates

First Submitted

January 23, 2017

First Submitted That Met QC Criteria

January 27, 2017

First Posted (Estimated)

January 30, 2017

Study Record Updates

Last Update Posted (Actual)

April 1, 2025

Last Update Submitted That Met QC Criteria

March 12, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • WVU010516

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

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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