Stereotactic Body Radiation Therapy With Immunotherapy for the Treatment of Mesothelioma

SBRT With Immunotherapy for Mesothelioma

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Pleural Mesothelial Neoplasm
• Intervention / Treatment: Other: Quality-of-Life Assessment; Radiation: Stereotactic Body Radiation Therapy; Other: Immunotherapy

Detailed Description

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.

TERTIARY OBJECTIVES:

I. To demonstrate that pre-treatment circulating tumor deoxyribonucleic acid (ctDNA) levels correlate with tumor burden in patients with solid tumors.

II. To investigate if ctDNA can robustly identify molecular residual disease (MRD) before clinical, radiographic or pathologic progression in patients with solid tumors treated with definitive-intent surgery +/- radiotherapy +/- chemotherapy.

III. To determine whether post-resection ctDNA levels can be used to predict the risk of tumor recurrence and response to adjuvant radiation or adjuvant chemoradiation in patients with solid tumors.

IV. To determine if ctDNA levels can predict disease response and/or disease recurrence before clinical, pathologic or radiographic response/progression is confirmed in patients with solid tumors.

V. To perform methylation sequencing of cell-free DNA to noninvasively determine ctDNA cell- of-origin.

VI. To perform cell-free ribonucleic acid (RNA) analysis to monitor gene expression changes and identify genomic rearrangements.

VII. To perform epigenetic and genetic analyses including methylation sequencing and single cell RNA sequencing on associated tumor and peripheral blood cell samples.

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.

OUTLINE:

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 6 weeks for 36 weeks or per clinician discretion, then every 3 months for 2 years or until disease progression or study exit, then yearly for up to 10 years.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (SBRT, immunotherapy); 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: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Radiation: Stereotactic Body Radiation Therapy; Undergo SBRT; Other Names: SBRT; SABR; Stereotactic Ablative Body Radiation Therapy; Other: Immunotherapy; Immunotherapy; Other Names: Immunological; Immunological Therapy; Immunologically Directed Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of treating patients with stereotactic body radiation therapy (SBRT) and immune checkpoint inhibitor	Feasibility of treating patients with SBRT and ICI will be determined by ability to treat all enrolled patients without meeting stopping rules (maintaining <30%toxicity).	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	Defined as the time from study entry to any progression or death.	Up to 2 years
Incidence of acute toxicity	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	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate	Will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST). The frequency and percentage of responses will be calculated.	Up to 2 years
Patterns of failure	Will be described descriptively as well using standard summary statistics (frequencies, percentages, etc.).	Up to 2 years
Quality of life (QOL)	Will be assessed using the Lung Cancer Symptom Scale (LCSS), which consists of nine questions assessing QOL in the past day. Questions are answered on a 10-point scale where 0=as good as it can be and 9=as bad as it can be. Lower score correspond to better QOL.	Baseline up to 2 years
T-cell receptor expression changes	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.	Baseline up to 2 years

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: William G. Breen, M.D., Mayo Clinic in Rochester

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2021
• Primary Completion (Estimated): May 25, 2026
• Study Completion (Estimated): May 25, 2026

Study Registration Dates

• First Submitted: May 21, 2021
• First Submitted That Met QC Criteria: June 8, 2021
• First Posted (Actual): June 15, 2021

Study Record Updates

• Last Update Posted (Estimated): October 22, 2025
• Last Update Submitted That Met QC Criteria: October 21, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenoma; Mesothelioma; Neoplasms, Mesothelial; Immunologic Factors; Physiological Effects of Drugs; Investigative Techniques; Therapeutics; Surgical Procedures, Operative; Pharmacologic Actions; Chemical Actions and Uses; Radiotherapy; Stereotaxic Techniques; Neurosurgical Procedures; Biological Therapy; Immunomodulation; Radiosurgery; Immunotherapy; Adjuvants, Immunologic
• Other Study ID Numbers: MC1924 (Other Identifier: Mayo Clinic in Rochester); NCI-2021-04302 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 19-012226 (Other Identifier: Mayo Clinic Institutional Review Board)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No