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

NCT05094544 | Withdrawn DMC FDA Device

• 1 other identifier: IIT-2020-POIMS-Lung
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Non-small Cell Lung Cancer

Keywords

Non-small cell lung cancer; SBRT

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• The impact of pre-surgical non-ablative SBRT on peri- and post-operative surgical complication rate

  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

  From Day of post-SBRT surgery through 6 month (± 2 months) post-operative follow up visit

• Loco-regional control disease

  From Day of enrollment through 36 month follow up visit

• Metastasis-free survival

  From Day of enrollment through 36 month follow up visit

• Overall survival

  From Day of enrollment through 36 month follow up visit

Study Arms (1)

Non-ablative SBRT

EXPERIMENTAL

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

Interventions

Non-ablative SBRT RADIATION

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

Non-ablative SBRT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Prior history of lung/chest wall surgery
• Prior chest radiation
• Prior immunotherapy
• History of autoimmune disease
• Currently using immunosuppressive drugs

Sponsors & Collaborators

• University of Kansas Medical Center: lead

Study Sites (1)

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Shalina Gupta-Burt, MD

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: September 1, 2021
• First Posted: October 26, 2021
• Study Start: October 1, 2021
• Primary Completion: March 23, 2023
• Study Completion: March 23, 2023
• Last Updated: December 12, 2024

Record last verified: 2022-03

Locations

US (1)