Stereotactic Body Radiation Therapy With Immunotherapy for the Treatment of Mesothelioma

Primary Outcome Measures

1. Feasibility of treatment of patients with stereotactic body radiation therapy (SBRT) without meeting stopping rules [ Time Frame: Up to 12 months ]
   treatment will be considered feasible if the stopping rules are not met. The stopping rule will be met if either A) 3 or more of the first 10 patients (or 30 percent or more of all patients after 10 are accrued) experience a Grade 4 AE, or B) 2 or more experience a Grade 5 AE at any time.
2. Feasibility of treatment of patients with immune checkpoint inhibitor (ICI) without meeting stopping rules [ Time Frame: Up to 12 months ]
   treatment will be considered feasible if the stopping rules are not met. The stopping rule will be met if either A) 3 or more of the first 10 patients (or 30 percent or more of all patients after 10 are accrued) experience a Grade 4 AE, or B) 2 or more experience a Grade 5 AE at any time.

Secondary Outcome Measures

1. Progression-free survival (PFS) [ Time Frame: From study entry to any progression or death, assessed up to 12 months ]
   Will be estimated using the Kaplan-Meier method.
2. Incidence of acute toxicity [ Time Frame: Up to 90 days post-SBRT ]
   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.
3. Incidence of late toxicity [ Time Frame: Up to 90 days post-SBRT ]
   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.

Other Outcome Measures

1. Overall survival (OS) [ Time Frame: From study entry to death from any cause, assessed up to 12 months ]
   Will be estimated using the Kaplan-Meier method.
2. Response rate [ Time Frame: Up to 12 months ]
   The confirmed response rate (by Response Evaluation Criteria in Solid Tumors) will be assessed. The confirmed response rate frequency of responses will be calculated.
3. Response rate [ Time Frame: Up to 12 months ]
   The confirmed response rate (by Response Evaluation Criteria in Solid Tumors) will be assessed. The confirmed response rate percentage of responses will be calculated.
4. Patterns of failure [ Time Frame: Up to 12 months ]
   Will be described descriptively as well using standard summary statistics (percentages).
5. Quality of life (QOL) questionnaire [ Time Frame: Baseline up to 12 months ]
   Will be assessed descriptively in these patients. Standard paired tests (paired t-test or the non-parametric equivalent) will be used to test for significance in QOL. Graphical and statistical methods will be used to summarize this data descriptively.
6. Correlation of T-cell receptor expression changes with outcomes [ Time Frame: Baseline up to 12 months ]
   Will correlate changes with outcomes (PFS, OS, response, etc.). Potential predictive and prognostic biomarkers using various assays including flow cytometry assays, quality and quantitative analysis of patients’ blood to explore associations with all primary and secondary endpoints will also be evaluated. Due to the limited sample size, these analyses will be hypothesis generating and descriptive in nature. Descriptive statistics will be summarized and the blood and tissue marker data will be correlated with clinical endpoints (PFS, OS, response, etc.). For time-to-event data, the Kaplan-Meier method will be used. For categorical data, will use the Fisher’s exact test. For biomarker data used to predict binary outcomes (i.e. response versus no response), will use logistic regression models.

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