SBRT + Checkpoint Inhibitors for Cancer

Recruiting at 11 trial locations

Overseen By Yoshiya Yamada, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Checkpoint inhibitors

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Active brain metastases, Autoimmune disease, Prior malignancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: Up to 24 weeks

69 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Drugs called checkpoint inhibitors help the immune system fight cancer. When the effectiveness of these drugs wears off, it may be possible to renew their effectiveness by combining it with a special type of radiation therapy called stereotactic body radiation therapy (SBRT). SBRT is a commonly used type of radiation therapy that gives high dose radiation with high precision to tumors in 1-5 treatments. Radiation therapy, such as SBRT can also treat sites of metastases. The use of checkpoint inhibitors in combination with SBRT has been suggested to improve the immune response against cancer but has not been tested in a formal clinical trial. Up to three lesions can be treated with SBRT. This study only allows checkpoint inhibitors that are already approved by the Federal Drug Agency (FDA) for the treatment of your disease. All radiation therapy will be done on machines which are FDA approved.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must stop taking immunosuppressive medications like steroids at least 14 days before starting the trial. You can continue taking immune checkpoint inhibitors if you are already on them.

Is the combination of SBRT and checkpoint inhibitors generally safe for humans?

Stereotactic ablative radiotherapy (SABR), a form of SBRT, has been used safely in treating various cancers, but some serious complications have been reported. Strategies to reduce these risks are important, and SABR has shown minimal toxicity in certain cases, like skull base tumors. However, concerns about high-grade toxic effects exist, especially when treating multiple metastases. ^{1 2 3 4 5}

How is the SBRT + Checkpoint Inhibitors treatment different from other cancer treatments?

SBRT combined with checkpoint inhibitors is unique because it uses precise, high-dose radiation to target tumors while simultaneously boosting the immune system's ability to fight cancer through drugs that block proteins like PD-1 and CTLA-4. This combination aims to enhance the body's immune response to cancer, potentially improving outcomes compared to using either treatment alone. ^{6 7 8 9 10}

What data supports the effectiveness of the treatment SBRT + Checkpoint Inhibitors for Cancer?

Research shows that combining stereotactic ablative radiotherapy (SABR) with immunotherapy can improve survival rates in certain types of lung cancer and metastatic diseases. SABR is effective in controlling tumors locally, and when combined with immunotherapy, it may enhance outcomes by reducing recurrence and improving overall survival. ^{11 12 13 14 15}

Who Is on the Research Team?

Yoshiya Yamada, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Adults with certain metastatic cancers (like melanoma, lung, bladder, renal, head/neck) who've been on approved checkpoint inhibitors for at least 2 months can join. They must have up to 5 progressing lesions and be able to continue immunotherapy post-radiation. Exclusions include active brain metastases, recent other treatments or severe allergies to monoclonal antibodies.

Inclusion Criteria

Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other study obligations

I can continue immune therapy after radiotherapy.

Your most recent scans show only a small amount of tumor growth, or up to 5 new or growing lesions. If you have more than 5 lesions, you can still join if the study doctors agree.

Exclusion Criteria

My brain cancer has been treated and stable for at least 8 weeks.

I do not have an active autoimmune disease, except for allowed conditions like vitiligo or type I diabetes.

I haven't taken steroids or immunosuppressants in the last 14 days, except for inhaled/topical ones or low-dose prednisone.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive stereotactic body radiation therapy (SBRT) to 1-3 lesions over 3 fractions

1-2 weeks

3 visits (in-person)

Treatment

Participants continue treatment with checkpoint inhibitors until progression or unacceptable toxicity

Up to 24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Ipilimumab
• Nivolumab
• Pembrolizumab
• Stereotactic Body Radiotherapy

Trial Overview The trial tests if high-precision radiation therapy (SBRT) can boost the effectiveness of FDA-approved checkpoint inhibitors like Ipilimumab, Nivolumab, Pembrolizumab or Atezolizumab in treating cancer that's started growing again.

How Is the Trial Designed?

Group I: Stereotactic Body Radiotherapy Experimental Treatment 2 Interventions

Image Guided, Stereotactic Body Radiotherapy (27 Gy over 3 fractions) to 1-3 lesions. Treatment with the checkpoint inhibitor will continue until progression at the discretion of the treating physician or unacceptable toxicity.

Stereotactic Body Radiotherapy is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Stereotactic Body Radiation Therapy for:

• Lung cancer
• Liver cancer
• Spine tumors
• Pancreatic cancer
• Prostate cancer

Approved in United States as Stereotactic Body Radiation Therapy for:

• Early-stage lung cancer
• Liver cancer
• Spine tumors
• Pancreatic cancer
• Prostate cancer

Approved in Canada as Stereotactic Body Radiation Therapy for:

• Lung cancer
• Liver cancer
• Spine tumors
• Pancreatic cancer
• Prostate cancer

Approved in Japan as Stereotactic Body Radiation Therapy for:

• Lung cancer
• Liver cancer
• Spine tumors
• Pancreatic cancer
• Prostate cancer

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

In a randomized phase 2 trial involving 156 participants, combining stereotactic ablative radiotherapy (SABR) with immunotherapy (I-SABR) significantly improved 4-year event-free survival from 53% to 77% for early-stage non-small-cell lung cancer (NSCLC), indicating a promising treatment strategy.

The I-SABR approach had manageable toxicity, with only 15% of participants experiencing grade 3 immunological adverse events related to nivolumab, and no severe adverse events associated with SABR, suggesting it is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy with or without immunotherapy for early-stage or isolated lung parenchymal recurrent node-negative non-small-cell lung cancer: an open-label, randomised, phase 2 trial. Chang, JY., Lin, SH., Dong, W., et al.[2023]

Stereotactic ablative radiotherapy (SABR) is the standard treatment for early-stage non-small-cell lung cancer that cannot be surgically removed, showing high rates of tumor control but facing challenges with regional and distant tumor failures.

Current research is exploring the use of immune checkpoint inhibitors as a systemic therapy option for patients treated with SABR, aiming to provide effective treatment with fewer side effects compared to traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inoperable Early-Stage Non-Small-Cell Lung Cancer: Stereotactic Ablative Radiotherapy and Rationale for Systemic Therapy. Daly, ME.[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]

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 31 patients with previously irradiated malignant skull base tumors treated with stereotactic ablative radiotherapy (SABR), the treatment demonstrated low toxicity, with no severe (grade 4 or 5) side effects reported.

The estimated 1-year overall survival rate was 35%, indicating that while SABR is well-tolerated, the survival outcomes for these patients remain limited, with a median time-to-progression of 3.3 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiosurgery for locally advanced or recurrent skull base malignancies with prior external beam radiation therapy. Xu, KM., Quan, K., Clump, DA., et al.[2020]

Stereotactic ablative radiotherapy (SABR) has rapidly expanded in clinical use for treating various primary and metastatic tumors, demonstrating promising results in tumor control.

Despite its effectiveness, SABR can lead to serious complications, highlighting the need for strategies to reduce these risks and improve the safety of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious complications associated with stereotactic ablative radiotherapy and strategies to mitigate the risk. Lo, SS., Sahgal, A., Chang, EL., et al.[2018]

Stereotactic ablative radiotherapy (SABR) for ultra-central lung tumors shows a high median local control rate of 96% at one year, indicating its effectiveness in managing these challenging lesions.

However, there is a significant risk of severe treatment-related toxicity, particularly in patients with endobronchial disease or those receiving high doses to the bronchial tree, highlighting the need for careful patient selection and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Effectiveness of Stereotactic Ablative Radiotherapy for Ultra-Central Lung Lesions: A Systematic Review. Chen, H., Laba, JM., Zayed, S., et al.[2020]

The introduction of stereotactic ablative body radiotherapy (SABR) for stage I non-small-cell lung cancer (NSCLC) at a Scottish cancer center has led to improved median survival rates, increasing from 32.5 months before SABR was available to 48.8 months after its establishment.

SABR has not only improved survival outcomes but also increased the proportion of patients receiving radical therapy, particularly among younger and healthier patients, indicating its effectiveness as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Impact of SABR on Stage I Non-Small-Cell Lung Cancer Outcomes at a Scottish Cancer Centre. Stares, M., Lewis, G., Vallet, M., et al.[2023]

In a study of 381 patients treated with stereotactic ablative body radiotherapy (SABR) for oligometastatic disease, the incidence of grade 3 or higher toxic effects was found to be less than 5%, indicating a favorable safety profile.

The rates of grade 2 or higher toxic effects were 18.6%, which is lower than the previously reported 29% in the SABR-COMET trial, suggesting that SABR may have acceptable toxicity levels and supports further research in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment With Stereotactic Ablative Radiotherapy for Up to 5 Oligometastases in Patients With Cancer: Primary Toxic Effect Results of the Nonrandomized Phase 2 SABR-5 Clinical Trial. Olson, R., Jiang, W., Liu, M., et al.[2023]

In a phase 1 trial involving 37 treatment-naive patients with stage IV NSCLC, combining concurrent stereotactic body radiotherapy (SBRT) with nivolumab and ipilimumab showed no dose-limiting toxicities, indicating a favorable safety profile for this multimodal treatment approach.

The study reported a median progression-free survival of 5.8 months and demonstrated that concurrent therapy was well tolerated, suggesting that this combination could effectively control metastasis in widely metastatic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1 Trial of Concurrent or Sequential Ipilimumab, Nivolumab, and Stereotactic Body Radiotherapy in Patients With Stage IV NSCLC Study. Bestvina, CM., Pointer, KB., Karrison, T., et al.[2022]

In a study of 68 patients with advanced solid tumors, the combination of stereotactic body radiotherapy (SBRT) followed by pembrolizumab showed a high one-year treated metastasis control rate of 89.5%, indicating effective tumor response regardless of whether the tumors received complete or partial radiation coverage.

The study found that treated metastasis control (TMC) was significantly associated with improved overall survival, and SBRT altered tumor gene expression by increasing immune-related genes while decreasing those related to cell cycle and DNA repair, suggesting a mechanism for enhanced immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved Survival Associated with Local Tumor Response Following Multisite Radiotherapy and Pembrolizumab: Secondary Analysis of a Phase I Trial. Luke, JJ., Onderdonk, BE., Bhave, SR., et al.[2021]

The addition of stereotactic body radiation therapy (SBRT) to checkpoint inhibitor (CPI) immunotherapy in 35 patients with metastatic non-small cell lung cancer was found to be safe, with no severe radiation-induced toxicities (grade 3 to 5) reported.

The combination treatment resulted in a best systemic objective response rate of 53%, indicating a promising efficacy that supports the need for further randomized trials to explore this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Prospective Trial Evaluating the Safety and Systemic Response From the Concurrent Use of Radiation Therapy with Checkpoint Inhibitor Immunotherapy in Metastatic Non-Small Cell Lung Cancer. Mattes, MD., Eubank, TD., Almubarak, M., et al.[2022]

Stereotactic body radiotherapy (SBRT) is effective for treating localized and metastatic prostate cancer, as prostate cancer shows increased sensitivity to higher radiation doses due to its low α/β ratio.

There is potential for combining SBRT with systemic therapies like androgen deprivation therapy (ADT) and immunotherapy, as SBRT may enhance immune responses, making it a promising area for ongoing research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Translating the Immunobiology of SBRT to Novel Therapeutic Combinations for Advanced Prostate Cancer. Adorno Febles, VR., Blacksburg, S., Haas, JA., et al.[2020]

Citations

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

Stereotactic ablative radiotherapy with or without immunotherapy for early-stage or isolated lung parenchymal recurrent node-negative non-small-cell lung cancer: an open-label, randomised, phase 2 trial. [2023]

2. 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]

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

Inoperable Early-Stage Non-Small-Cell Lung Cancer: Stereotactic Ablative Radiotherapy and Rationale for Systemic Therapy. [2022]

4. Ireland pubmed.ncbi.nlm.nih.gov

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

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

Stereotactic ablative radiosurgery for locally advanced or recurrent skull base malignancies with prior external beam radiation therapy. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Serious complications associated with stereotactic ablative radiotherapy and strategies to mitigate the risk. [2018]

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

Safety and Effectiveness of Stereotactic Ablative Radiotherapy for Ultra-Central Lung Lesions: A Systematic Review. [2020]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Real-World Impact of SABR on Stage I Non-Small-Cell Lung Cancer Outcomes at a Scottish Cancer Centre. [2023]

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

Treatment With Stereotactic Ablative Radiotherapy for Up to 5 Oligometastases in Patients With Cancer: Primary Toxic Effect Results of the Nonrandomized Phase 2 SABR-5 Clinical Trial. [2023]

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

A Phase 1 Trial of Concurrent or Sequential Ipilimumab, Nivolumab, and Stereotactic Body Radiotherapy in Patients With Stage IV NSCLC Study. [2022]

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

Improved Survival Associated with Local Tumor Response Following Multisite Radiotherapy and Pembrolizumab: Secondary Analysis of a Phase I Trial. [2021]

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

A Prospective Trial Evaluating the Safety and Systemic Response From the Concurrent Use of Radiation Therapy with Checkpoint Inhibitor Immunotherapy in Metastatic Non-Small Cell Lung Cancer. [2022]

14. Switzerland pubmed.ncbi.nlm.nih.gov

Translating the Immunobiology of SBRT to Novel Therapeutic Combinations for Advanced Prostate Cancer. [2020]

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

Combining Dual Checkpoint Immunotherapy with Ablative Radiation to All Sites of Oligometastatic Non-Small Cell Lung Cancer: Toxicity and Efficacy Results of a Phase Ib Trial. [2023]