Pre-Operative Immuno-Modulatory SBRT (POIMS Trial): A Pilot Trial in Early Stage NSCLC

Study Overview
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Brief Summary
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The current proposal is structured as a pilot trial to evaluate the impact of non-ablative SBRT (800 cGy X 3 fractions) as an immunomodulatory mechanism in patients with early stage NSCLC who are surgical candidates. Tumor, normal tissue and blood specimens will be analyzed for immunomodulatory changes including phenotypic changes in tumor cell surface marker expression, tumor and normal tissue microenvironment and gene expression profiles, serum/blood immune profile changes, and circulating tumor cell immunophenotypic and gene expression alterations. Published literature showed that cytotoxic doses of XRT may not elicit a clinically meaningful alteration in the immune profile. Further, studies using an animal model have concluded a fractionated regimen induces a greater abscopal effect than single dose radiation. Furthermore, research has shown a regimen of 800 cGy X 3 fractions yielded the most significant changes in the immune profile compared to 2000 cGy X 1 or 600 cGy X 5. The immune response within the tumor milieu is a complex dynamic process with an interplay among lymphocyte subsets, antigen presenting cells/dendritic cells, macrophages, and tumor cells. The interactions between the various components is orchestrated by a variety of extracellular and intracellular signaling pathways involving ligand and cell surface expression, cytokine release, and activation or inhibition of a variety of T cell subsets. In order to comprehensively define the immunomodulatory effect of three fractions of 800 cGy on the primary tumor, the investigators will analyze the following: tumor cell surface phenotype, tumor microenvironment immune profile and gene expression profile, T cell repertoire changes in tumor tissue and peripheral blood, and circulating tumor cell phenotype and gene expression profiles. Each of these components has been shown to be impacted by radiation in either a cell culture or animal model systems. By characterizing, quantitating and defining these changes related to three fractions of 800 cGy, it will directly provide important insights to inform rational uses of XRT and immunotherapy in the future.

Official Title
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Pre-Operative Immuno-Modulatory SBRT (POIMS Trial): A Pilot Trial in Early Stage NSCLC

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Radiation: Non-ablative SBRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stage I-II NSCLC Adequate diagnostic biopsy tissue to allow pre-SBRT tumor analysis Candidate for oncologic surgery (lobectomy or sub lobar resection) for the lung cancer Lesion located peripherally, ≥ 2 cm from bronchial margin, and 1 cm from visceral pleura, with location deemed acceptable by cardio-thoracic surgeon for resection. Adequate pulmonary function test results Exclusion Criteria: Prior history of lung/chest wall surgery Prior chest radiation Prior immunotherapy History of autoimmune disease Currently using immunosuppressive drugs

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: Non-ablative SBRT<br>Non-ablative SBRT (800 cGy X 3 fractions) given 5-7 days preoperatively in selected patients with stage I-II NSCLC | Radiation: Non-ablative SBRT<br>* Non-ablative SBRT (800 cGy X 3 fractions) given 5-7 days preoperatively in selected patients with stage I-II NSCLC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in tumor T cell repertoire following pre and post SBRT | Pre and post study intervention biopsy tissue comparison | through study completion, an average of 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The impact of pre-surgical non-ablative SBRT on peri- and post-operative surgical complication rate | Medical Record Review Clavien-Dindo Classification system | From Day of post-SBRT surgery through 6 month (± 2 months) post-operative follow up visit | 
| Impact of SBRT on post-surgical wound healing complication rate assessed by CTCAE v5 | Medical record review General Thoracic Surgery Database. | From Day of post-SBRT surgery through 6 month (± 2 months) post-operative follow up visit | 
| Loco-regional control disease | Medical record review Loco-regional metastasisi | From Day of enrollment through 36 month follow up visit | 
| Metastasis-free survival | Medical record review | From Day of enrollment through 36 month follow up visit | 
| Overall survival | Medical record review | From Day of enrollment through 36 month follow up visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-small cell lung cancer, SBRT