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

Non-small Cell Lung Cancer Clinical Trial

— POIMS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05094544
• Other study ID #: IIT-2020-POIMS-Lung
• Status: Recruiting
• Phase: N/A
• Start date: October 1, 2021
• Est. completion date: April 2026

Study information

• Verified date: March 2022
• Source: University of Kansas Medical Center
• Contact: Shalina Gupta-Burt, MD
• Phone: 913-588-3600
• Email: sguptaburt[@]kumc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: April 2026
• Est. primary completion date: April 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Non-small Cell Lung Cancer

Intervention

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

Locations

Country	Name	City	State
United States	University of Kansas Medical Center	Kansas City	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
University of Kansas Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Loco-regional control disease	Medical record review; Loco-regional metastasisi	From Day of enrollment through 36 month follow up visit
Secondary	Metastasis-free survival	Medical record review	From Day of enrollment through 36 month follow up visit
Secondary	Overall survival	Medical record review	From Day of enrollment through 36 month follow up visit