Stereotactic Body Radiation Therapy With Immunotherapy for the Treatment of Mesothelioma

Study Overview
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Brief Summary
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This phase I trial studies the effect of stereotactic body radiation therapy and immunotherapy in treating patients with mesothelioma. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving stereotactic body radiation therapy and immunotherapy may improve the tumors response to the treatment and decrease side-effects.

Detailed Description
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PRIMARY OBJECTIVE: I. To determine the feasibility of focal stereotactic body radiation therapy (SBRT) with immune check inhibitors (ICI) for treatment of mesothelioma. SECONDARY OBJECTIVES: I. To determine progression free survival in patients treated with SBRT and ICI. II. To assess acute and late toxicities overall in patients treated with SBRT and ICI. EXPLORATORY OBJECTIVES: I. To determine overall survival in these patients. II. To estimate the objective response rate (ORR) using immune-modified Response Evaluation Criteria in Solid Tumors (iRECIST) 1.1 criteria. III. To describe patterns of failure. IV. To estimate the quality of life (QOL) in these patients. V. Determine whether T-cell receptor expression changes during and after immunotherapy and SBRT, and whether these changes correlate with outcomes. VI To evaluate potential predictive and prognostic biomarkers using various assays including flow cytometry assays, qualitative and quantitative analyses of patients' blood to explore associations with all primary and secondary endpoints. OUTLNE: Patients undergo 3-5 daily fractions of SBRT in the absence of disease progression or unacceptable toxicity. Patients also receive immunotherapy at the discretion of the treating medical oncologist. After completion of study treatment, patients are followed up every 3 months for up to 12 months.

Official Title
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SBRT With Immunotherapy for Mesothelioma

Conditions
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Pleural Mesothelial Neoplasm

Intervention / Treatment
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* Other: Immunotherapy
* Other: Quality-of-Life Assessment
* Radiation: Stereotactic Body Radiation Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >= 18 years Histological confirmation of pleural mesothelioma Measurable disease Eastern Cooperative Oncology Group (ECOG) performance status (PS) =< 2 Negative pregnancy test done =< 14 days prior to registration, for women of childbearing potential only. NOTE: male/female: Must be willing to use birth control for the entire study and must agree to use one of the following birth control methods listed: Hormonal methods, such as birth control pills, patches, injections, vaginal ring, or implants Barrier methods (such as a condom or diaphragm) used with a spermicide (a foam, cream, or gel that kills sperm) Intrauterine device (IUD) Abstinence (no sex) Provide written informed consent Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study) Willing to provide blood samples for correlative research purposes Patient has received or is planning to receive ICI for mesothelioma Patient is planning to receive SBRT (stereotactic body radiation therapy) for mesothelioma Exclusion Criteria: Any of the following: Pregnant women Nursing women

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: Treatment (SBRT, immunotherapy)<br>Patients undergo 3-5 daily fractions of SBRT in the absence of disease progression or unacceptable toxicity. Patients also receive immunotherapy at the discretion of the treating medical oncologist. | Other: Immunotherapy<br>* Immunotherapy<br>* Other names: Immunologically Directed Therapy;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Radiation: Stereotactic Body Radiation Therapy<br>* Undergo SBRT<br>* Other names: Stereotactic Ablative Body Radiation Therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of treating patients with stereotactic body radiation therapy (SBRT) and immune checkpoint inhibitor |  | Up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | Will be estimated using the Kaplan-Meier method. | From study entry to any progression or death, assessed up to 12 months | 
| Incidence of acute toxicity | These adverse events (AEs) will be shown via frequency tables and percentages. The maximum grade for each type of adverse event will be summarized using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Will assess and summarize all acute and late AE's, regardless of attribution. | Up to 90 days post-SBRT | 
| Incidence of late toxicity | These AEs will be shown via frequency tables and percentages. The maximum grade for each type of adverse event will be summarized using CTCAE version 5.0. Will assess and summarize all acute and late AE's, regardless of attribution. | Up to 90 days post-SBRT |