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

Not Applicable

Completed

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Radiation Therapy + Immunotherapy	Radiation	3-5 fraction course of radiation therapy to target lesion concurrent with an immuno-therapeutic agent
Radiation Therapy + Immunotherapy	Immuno-Therapeutic Agent	3-5 fraction course of radiation therapy to target lesion concurrent with an immuno-therapeutic agent

Primary Outcome Measures

Name	Time	Method
Time to Best Overall Response	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.

Secondary Outcome Measures

Name	Time	Method
Time to Progression Free Survival	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).
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.