SBRT + Immunotherapy for Mesothelioma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Mayo Clinic

Must be taking: ICI

Disqualifiers: Pregnancy, Nursing

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a combination of targeted radiation therapy and immunotherapy to treat mesothelioma, a cancer affecting the lung lining. The goal is to determine if this approach can enhance tumor response and reduce side effects. The trial employs a precision radiation method that targets tumors directly, potentially minimizing harm to healthy tissues. Suitable candidates have mesothelioma and are either planning to receive or have received immune-based treatments. Participants must also be prepared to undergo specific radiation therapy as part of the study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

Do I have to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that stereotactic body radiation therapy (SBRT) is generally safe, with a low risk of harmful side effects. It effectively targets tumors precisely, helping to protect nearby healthy tissue.

Regarding immunotherapy, evidence suggests it can be safe for mesothelioma patients. In one study, over 80% of patients experienced no major problems and could continue treatment. Immunotherapy has shown promise, with some patients living longer than those who received traditional chemotherapy.

Both treatments have been studied separately and appear well-tolerated. However, since this trial is in an early phase, it primarily focuses on safety. Researchers are still learning about any potential side effects when these treatments are combined. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for mesothelioma, which typically include surgery, chemotherapy, and conventional radiation therapy, this new approach combines immunotherapy with Stereotactic Body Radiation Therapy (SBRT). Researchers are excited because SBRT delivers high doses of radiation precisely to tumors over just a few sessions, potentially reducing damage to surrounding healthy tissue and shortening treatment time. Additionally, pairing SBRT with immunotherapy, which harnesses the body’s immune system to fight cancer, may enhance the overall effectiveness by targeting cancer cells in a more comprehensive way. This combination could offer a synergistic effect, potentially leading to better outcomes for patients with mesothelioma.

What evidence suggests that this trial's treatments could be effective for mesothelioma?

Research has shown that stereotactic body radiation therapy (SBRT) can effectively treat mesothelioma. Studies have found that SBRT is generally well-tolerated and can shrink tumors while minimizing harm to healthy tissue. In some cases, it has even extended patients' lives compared to those with similar cancers.

For immunotherapy, research suggests it holds promise for mesothelioma. Patients who received immunotherapy have shown better survival rates than those who underwent traditional chemotherapy. Specifically, some reports indicate a 41% survival rate over two years with immunotherapy, compared to 27% with chemotherapy. In this trial, participants will receive both SBRT and immunotherapy, potentially offering a powerful approach to fighting mesothelioma by attacking tumors in different ways. ^{2 4 5 6 7}

Who Is on the Research Team?

William G. Breen, M.D.

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

Adults with confirmed pleural mesothelioma, who can undergo stereotactic body radiation therapy (SBRT) and immunotherapy. Participants must be able to give consent, follow up at the institution, have an ECOG performance status of ≤2, not be pregnant or nursing, and agree to use effective birth control.

Inclusion Criteria

I am planning to undergo SBRT for mesothelioma.

Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)

Must be willing to use birth control for the entire study and must agree to use one of the following birth control methods: Hormonal methods, barrier methods used with a spermicide, intrauterine device (IUD), abstinence

Exclusion Criteria

I am currently breastfeeding.

Pregnant women

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo 3-5 daily fractions of SBRT and receive immunotherapy at the discretion of the treating medical oncologist

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Immunotherapy
• Stereotactic Body Radiation Therapy

Trial Overview

The trial is testing how well patients with mesothelioma respond to a combination of high-precision radiation therapy called SBRT and immune-boosting treatments known as immunotherapy. The goal is to see if this combo improves tumor response while minimizing side effects.

How Is the Trial Designed?

Group I: Treatment (SBRT, immunotherapy) Experimental Treatment 3 Interventions

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.

Immunotherapy is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Various Immunotherapies for:

• Melanoma
• Non-Hodgkin lymphoma
• Chronic myelogenous leukemia (CML)
• Kidney cancer
• Breast cancer
• Prostate cancer

Approved in United States as Various Immunotherapies for:

• Melanoma
• Non-Hodgkin lymphoma
• Chronic myelogenous leukemia (CML)
• Kidney cancer
• Breast cancer
• Prostate cancer
• Bladder cancer

Approved in Canada as Various Immunotherapies for:

• Melanoma
• Non-Hodgkin lymphoma
• Chronic myelogenous leukemia (CML)
• Kidney cancer
• Breast cancer
• Prostate cancer

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Stereotactic ablative radiotherapy (SABR) is a highly effective and low-toxicity treatment for metastatic tumors, achieving local control rates of about 80%.

SABR shows promise in treating oligometastatic patients, with pilot studies suggesting it may be 'curative' in 20-25% of cases, especially when combined with systemic therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New concepts and insights into the role of radiation therapy in extracranial metastatic disease. Ricardi, U., Filippi, AR., Franco, P.[2013]

The iSABR trial demonstrated that individualized stereotactic ablative radiotherapy (SABR) for lung tumors resulted in high local control rates, with freedom from local recurrence at 1 year ranging from 94% to 97% across different patient groups.

The trial showed a low incidence of severe toxic effects (only 5%), indicating that personalized dosing strategies can minimize risks while maintaining effective treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Individualized Stereotactic Ablative Radiotherapy for Lung Tumors: The iSABR Phase 2 Nonrandomized Controlled Trial. Gensheimer, MF., Gee, H., Shirato, H., et al.[2023]

Stereotactic ablative radiotherapy (SABR) may enhance the immune response in patients with non-small cell lung cancer (NSCLC) when combined with immune checkpoint inhibitors, potentially improving treatment outcomes.

Recent studies, including prospective trials, suggest that this combination therapy could lead to better survival rates compared to traditional palliative radiotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation and immunotherapy combinations in non-small cell lung cancer. Azghadi, S., Daly, ME.[2021]

Stereotactic body radiation therapy (SBRT) for unresectable pancreatic cancer showed similar overall survival and disease control outcomes compared to conventional intensity modulated radiation therapy (IMRT), based on a retrospective review of 270 patients (44 SBRT and 226 IMRT).

SBRT was associated with significantly lower rates of acute gastrointestinal toxicity, fatigue, and hematologic toxicity compared to IMRT, indicating that SBRT may be a safer and more tolerable treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation vs. intensity-modulated radiation for unresectable pancreatic cancer. Park, JJ., Hajj, C., Reyngold, M., et al.[2022]

In a study of 100 patients with early-stage non-small cell lung cancer (NSCLC) treated with stereotactic ablative body radiotherapy (SABR), the 1-, 2-, and 3-year local control rates were 100%, 93.55%, and 84.33%, respectively, indicating high efficacy in tumor control.

The treatment was associated with low toxicity, with only 2% of patients experiencing Grade-3 side effects, suggesting that SABR is a safe option for patients who are inoperable or refuse surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Definitive Treatment of Early-Stage Non-Small Cell Lung Cancer with Stereotactic Ablative Body Radiotherapy in a Community Cancer Center Setting. Heal, C., Ding, W., Lamond, J., et al.[2020]

Stereotactic ablative radiotherapy (SABR) using Cyberknife demonstrated high effectiveness in treating stage I non-small-cell lung cancer, with 2-year local control, progression-free, and overall survival rates of 91.9%, 61.7%, and 84.8%, respectively, based on a study of 153 patients.

The treatment was generally safe, with only 8.1% of patients experiencing severe toxicities, including one case of grade 5 radiation pneumonitis, indicating that while SABR is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Radiotherapy Using CyberKnife for Stage I Non-small-cell Lung Cancer: A Retrospective Analysis. Hayashi, K., Suzuki, O., Shiomi, H., et al.[2022]

In a study of 106 patients with early-stage non-small cell lung cancer treated with CyberKnife® SBRT, the treatment demonstrated an 88% local control rate at 2 years, indicating its efficacy in managing this type of cancer.

The treatment was associated with low toxicity, with only 20% of patients experiencing mild fatigue and 17% mild dyspnea, and only 4% experiencing significant late effects, suggesting it is a safe option for medically inoperable patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk-adapted robotic stereotactic body radiation therapy for inoperable early-stage non-small-cell lung cancer. Temming, S., Kocher, M., Stoelben, E., et al.[2022]

In a phase II trial involving 106 patients with metastatic cancers, the combination of ipilimumab and stereotactic ablative radiotherapy (SABR) showed promising long-term survival rates, with 5-year overall survival rates of 15%.

Patients receiving SABR targeting lung metastases had significantly better overall survival (18.67 months) and progression-free survival (6.87 months) compared to those with liver metastases, highlighting the importance of tumor location in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year overall survival with ipilimumab and stereotactic ablative radiotherapy for metastatic disease. He, K., Hong, DS., Tang, C., et al.[2023]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7082257/

Immunotherapy for mesothelioma: a critical review of current ...

While the data remains immature, it has been reported that 1-year OS was 65% at a median follow-up of 14.4 months (42). While this suggests suggests that a ...

2.

asbestos.com

asbestos.com/treatment/immunotherapy/

Mesothelioma Immunotherapy: Success Rates & FDA ...

Mesothelioma patients who underwent immunotherapy have a 41% 2-year survival rate, compared to 27% with chemotherapy. Opdivo and Yervoy provide an average ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11853238/

Recent Advances in Mesothelioma Treatment: Immunotherapy ...

This combination therapy achieved a median OS of 20.4 months compared to 12.1 months in the historical chemotherapy-only control, with an estimated 12-month OS ...

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S2212534525000012

Review Current drug therapy for pleural mesothelioma

A meta-analysis evaluated data from 13 trials involving 888 patients who received treatment with anti-PD-L1/anti-PD-1 agents. The ORR and DCR were 18.1% and ...

5.

jto.org

jto.org/article/S1556-0864(24)00037-6/fulltext

Immunotherapy Is a Good Standard Option for Patients ...

The immunotherapy group had an overall survival (OS) benefit of 18.1 versus 14.1 months for the chemotherapy group. The hazard ratio was 0.74. Of interest is ...

6.

hopkinsmedicine.org

hopkinsmedicine.org/news/newsroom/news-releases/2025/09/first-ever-clinical-trial-demonstrates-safety-molecular-readout-and-promise-of-pre-and-post-surgery-immunotherapy-combination-for-patients-with-operable-mesothelioma

First-Ever Clinical Trial Demonstrates Safety, Molecular ...

In the phase 2 trial, over 80% of patients successfully underwent surgery within the preplanned window after receiving neoadjuvant immunotherapy ...

7.

sciencedirect.com

sciencedirect.com/science/article/pii/S266636432400105X

Real-World Outcomes of Patients With Malignant Pleural ...

Twenty-five patients (40%) died without further treatment after 2L+ ipi-nivo, 28 patients (45%) patients received further systemic therapy, mostly single-agent ...