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

20 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment SBRT + Immunotherapy for Mesothelioma?

Research on similar treatments, like the combination of stereotactic ablative radiotherapy (SABR) and immunotherapy in non-small cell lung cancer (NSCLC), shows that this approach can enhance survival and has a synergistic effect. Additionally, SABR has been effective in controlling tumors in various cancers, with local control rates of about 80%, suggesting potential benefits when combined with immunotherapy. ^{1 2 3 4 5}

Is the combination of SBRT and immunotherapy generally safe for humans?

Studies show that stereotactic body radiation therapy (SBRT), also known as stereotactic ablative radiotherapy (SABR), is generally safe for treating lung cancer, with some risk of toxic effects. When combined with immunotherapy like ipilimumab, it has shown low toxicities in treating metastatic cancers. ^{2 6 7 8 9}

How is the SBRT + Immunotherapy treatment for mesothelioma different from other treatments?

The combination of Stereotactic Body Radiation Therapy (SBRT) and Immunotherapy for mesothelioma is unique because it aims to enhance the immune response against cancer by using radiation to expose tumor antigens, potentially improving outcomes through the abscopal effect, where tumors respond even in nonradiated areas. ^{10 11 12 13 14}

What is the purpose of this trial?

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.

Research Team

William G. Breen, M.D.

Principal Investigator

Mayo Clinic in Rochester

Eligibility Criteria

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.

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

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

Exclusion Criteria

I am currently breastfeeding.

Pregnant women

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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) 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Radiation and immunotherapy combinations in non-small cell lung cancer. [2021]

2. Ireland pubmed.ncbi.nlm.nih.gov

Five-year overall survival with ipilimumab and stereotactic ablative radiotherapy for metastatic disease. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Alliance A082002 -a randomized phase II/III trial of modern immunotherapy-based systemic therapy with or without SBRT for PD-L1-negative, advanced non-small cell lung cancer. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Radio Therapy (SABR) followed by immunotherapy a challenge for individualized treatment of metastatic solid tumours. [2021]

5. England pubmed.ncbi.nlm.nih.gov

New concepts and insights into the role of radiation therapy in extracranial metastatic disease. [2013]

6. Switzerland 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. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Individualized Stereotactic Ablative Radiotherapy for Lung Tumors: The iSABR Phase 2 Nonrandomized Controlled Trial. [2023]

8. Greece pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Radiotherapy Using CyberKnife for Stage I Non-small-cell Lung Cancer: A Retrospective Analysis. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Risk-adapted robotic stereotactic body radiation therapy for inoperable early-stage non-small-cell lung cancer. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Predictors of Pneumonitis in Combined Thoracic Stereotactic Body Radiation Therapy and Immunotherapy. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Effect of Immunotherapy and Stereotactic Body Radiation Therapy Sequencing on Local Control and Survival in Patients With Spine Metastases. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy and immunotherapy. [2020]

13. Germany pubmed.ncbi.nlm.nih.gov

Dose coverage impacts local control in ultra-central lung oligometastases treated with stereotactic radiotherapy. [2021]

14. England pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation vs. intensity-modulated radiation for unresectable pancreatic cancer. [2022]