Hypofractionated Radiation Therapy to Improve Immunotherapy Response in Non-Small Cell Lung Cancer
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
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 Design
Arms and Interventions
| 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:
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:
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Outcome Measures
Primary Outcome Measures
- Best Overall Response [From the start of treatment until disease progression up to 2 years.]
Best overall response rate (complete and partial), measured on follow-up imaging as per immune-related Response Criteria (irRC) approx. every three months taking the smallest measurement recorded.
Secondary Outcome Measures
- Progression Free Survival [From the start of treatment until the date of documented progression or death assessed up to 2 years]
Disease status will be evaluated based on imaging results until progression or death; assessed every three months.
- Overall Survival [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.
- Adverse event evaluation [From the time of consent at 3 month intervals until 1 year after treatment has stopped or death]
Adverse event will be recorded and graded based on CTCAE version 4
- Quality of Life Assessment FACT-L [3 month intervals from the start of treatment until progression up to 2 years]
Access change in quality of life scores between visits using the FACT-L score. A difference of 3 points will be considered clinically significant.
- Quality of Life Assessment FACT-Fatigue [3 month intervals from the start of treatment until progression up to 2 years]
Access change in quality of life between visits using the FACT- Fatigue scores. A difference of 3 points will be considered clinically significant.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Stage IV metastatic Non Small Cell Lung Cancer
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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.
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History of prior cytotoxic chemotherapy (with or without concomitant radiation therapy) with subsequent distant (metastatic) disease relapse, or progression of disease while on chemotherapy.
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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.
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Life expectancy greater than 3 months
Exclusion Criteria:
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Active autoimmune disease, primary immunodeficiency syndrome, HIV/AIDS, or hepatitis B or C
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Oral corticosteroid dependency
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Uncontrolled or untreated active brain metastases/CNS disease
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Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | WVU Cancer Institute - Mary Babb Randolph Cancer Center | Morgantown | West Virginia | United States | 26506 |
Sponsors and Collaborators
- West Virginia University
- West Virginia Clinical and Translational Science Institute
Investigators
- Principal Investigator: Joshua Weir, MD, WVUCI - Mary Babb Randolph Cancer Center
Study Documents (Full-Text)
More Information
Publications
None provided.- WVU010516