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

NCT ID: NCT03035890

Last Updated: 2025-04-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-23
• Study Completion Date: 2022-06-30

Brief Summary

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.

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.

Conditions

Non Small Cell Lung Cancer Metastatic

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Radiation Therapy + Immunotherapy

3-5 fraction course of radiation therapy to target lesion concurrent with an immuno-therapeutic agent

Group Type: EXPERIMENTAL

Radiation

Intervention Type: 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)

Immuno-Therapeutic Agent

Intervention Type: DRUG

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.

Interventions

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)

Intervention Type: RADIATION

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.

Intervention Type: DRUG

Other Intervention Names

Hypofractionated Radiation; Immunotherapy

Eligibility Criteria

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

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

Sponsors

West Virginia Clinical and Translational Science Institute

OTHER

Sponsor Role: collaborator

West Virginia University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mohammad Shaikh, MD

Role: PRINCIPAL_INVESTIGATOR

West Virginia University

Locations

WVU Cancer Institute - Mary Babb Randolph Cancer Center

Morgantown, West Virginia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

WVU010516

Identifier Type: -

Identifier Source: org_study_id