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

Study Overview
=================
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.

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

Conditions
-----------------
Non Small Cell Lung Cancer Metastatic

Intervention / Treatment
-----------------
* Radiation: Radiation
* Drug: Immuno-Therapeutic Agent


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Radiation Therapy + Immunotherapy<br>3-5 fraction course of radiation therapy to target lesion concurrent with an immuno-therapeutic agent | Radiation: Radiation<br>* 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)<br>* Other names: Hypofractionated Radiation;Drug: Immuno-Therapeutic Agent<br>* 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.<br>* Other names: Immunotherapy;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Response | 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. | From the start of treatment until disease progression up to 2 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Disease status will be evaluated based on imaging results until progression or death; assessed every three months. | From the start of treatment until the date of documented progression or death assessed up to 2 years | 
| Overall Survival | 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 | 
| Adverse event evaluation | Adverse event will be recorded and graded based on CTCAE version 4 | From the time of consent at 3 month intervals until 1 year after treatment has stopped or death | 
| Quality of Life Assessment FACT-L | Access change in quality of life scores between visits using the FACT-L score. A difference of 3 points will be considered clinically significant. | 3 month intervals from the start of treatment until progression up to 2 years | 
| Quality of Life Assessment FACT-Fatigue | Access change in quality of life between visits using the FACT- Fatigue scores. A difference of 3 points will be considered clinically significant. | 3 month intervals from the start of treatment until progression up to 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
NSCLC, Lung Cancer, Non Small Cell Lung Cancer