Liver SBRT in Combination With Immune Checkpoint Inhibition in Patients With Metastatic Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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Determine the feasibility of liver stereotactic body radiation therapy (SBRT) given in combination with systemic therapy (immune checkpoint inhibitors) in adult patients with metastatic NSCLC with liver metastases.

Official Title
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Phase I Trial of Feasibility and Safety of Liver SBRT in Combination With Immune Checkpoint Inhibition in Patients With Metastatic Non-small Cell Lung Cancer

Conditions
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Liver Metastases, Non-small Cell Lung Cancer

Intervention / Treatment
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* Radiation: Liver SBRT
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients (≥18 years of age) Histologically or cytologically confirmed NSCLC with liver metastases Eligible for immune checkpoint inhibitors per treating medical oncologist Disease must be measurable per RECIST criteria ECOG Performance status of 0 - 2 Adequate organ function per protocol. Allowable prior therapy includes adjuvant durvalumab, prior radiotherapy outside the upper abdomen. Patients must be willing and able to sign an informed consent form. Participants of childbearing potential willing to undergo pregnancy test and use contraception per Appendix. Exclusion Criteria: Liver tumor burden which cannot be targeted with SBRT per treating radiation oncologist Presence of uncontrolled intercurrent illness or significant comorbidities precluding participation in a clinical study as determined by investigator Diagnosis of underlying parenchymal end stage liver disease (cirrhosis) or biliary disease (primary biliary cirrhosis). Other invasive malignancy active within 1 years, excluding in situ cancers Presence of psychiatric or substance abuse disorders that would interfere with compliance or safety Has a known history of active Bacillus Tuberculosis (TB), Hepatitis B or Hepatitis C infection Has received a live (active) vaccine within 30 days of enrollment. Active autoimmune disease that has required systemic treatment in the past 1 years aside from hormone replacement therapy (ie. thyroxine, insulin, or physiologic corticosteroid replacement therapy) Baseline corticosteroid use (>10 mg prednisone daily or equivalent) at study entry Pregnancy or breast feeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>This is an open-label, single-arm, single center clinical trial to evaluate the feasibility of liver SBRT (up to 4 metastases) during the first cycle of physician's choice ICI for NSCLC. | Radiation: Liver SBRT<br>* 24-45 Gy delivered in 3-5 fractions to 1-4 lesions.<br>Drug: Pembrolizumab<br>* 200 mg every 3 weeks or 400 mg every 6 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients who receive all fractions of radiotherapy as planned | Feasibility determination. Analyzed with descriptive statistics. | Up to 0.5 years after start of study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who develop grade 3 or higher toxicity | Any serious adverse event that occurs within 60 days after treatment with SBRT or after this time frame and is considered related to the study treatment will also be reported. Analyzed with descriptive statistics. | Up to 1 year after start of study treatment | 
| Progression-free survival | PFS defined as the time from start of treatment to date of radiological or clinical progression (leading to withdrawal from the study), or death from any cause, whichever comes first. Assessed Per RECIST v1.1; analyzed using Kaplan-Meier curves and descriptive statistics. | Time Frame: Up to 3 years after end of study treatment | 
| Overall survival (OS) | OS defined as the time from start of treatment to death. This will be analyzed using Kaplan-Meier curves and descriptive statistics. | Time Frame: Up to 3 years after end of study treatment | 
| Proportion of patients with local control | Freedom from local progression (local control) is defined as the lack of progression of the tumors treated by RT, either by tumor size or enhancement. Progression or development of new tumors elsewhere in the liver or outside of the liver would not constitute a local control failure. Tumors which increase in size or demonstrate new or increasing enhancement are considered progression. Analyzed using Kaplan-Meier curves and descriptive statistics. | Time Frame: Up to 3 years after end of study treatment |