69 Participants Needed

SBRT + Checkpoint Inhibitors for Cancer

Recruiting at 11 trial locations
MV
YY
Overseen ByYoshiya Yamada, MD
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: Memorial Sloan Kettering Cancer Center
Must be taking: Checkpoint inhibitors
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 4 JurisdictionsThis treatment is already approved in other countries

Trial Summary

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.

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.12345

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.678910

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.1112131415

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.

Research Team

YY

Yoshiya Yamada, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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.
See 6 more

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.
See 6 more

Timeline

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

Treatment Details

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.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Stereotactic Body RadiotherapyExperimental Treatment2 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

Find a Clinic Near You

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials
1,998
Recruited
602,000+

Findings from Research

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

References

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]
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]
Inoperable Early-Stage Non-Small-Cell Lung Cancer: Stereotactic Ablative Radiotherapy and Rationale for Systemic Therapy. [2022]
Five-year overall survival with ipilimumab and stereotactic ablative radiotherapy for metastatic disease. [2023]
New concepts and insights into the role of radiation therapy in extracranial metastatic disease. [2013]
Stereotactic ablative radiosurgery for locally advanced or recurrent skull base malignancies with prior external beam radiation therapy. [2020]
Serious complications associated with stereotactic ablative radiotherapy and strategies to mitigate the risk. [2018]
Safety and Effectiveness of Stereotactic Ablative Radiotherapy for Ultra-Central Lung Lesions: A Systematic Review. [2020]
Real-World Impact of SABR on Stage I Non-Small-Cell Lung Cancer Outcomes at a Scottish Cancer Centre. [2023]
10.United Statespubmed.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 Statespubmed.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 Statespubmed.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 Statespubmed.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]
Translating the Immunobiology of SBRT to Novel Therapeutic Combinations for Advanced Prostate Cancer. [2020]
15.United Statespubmed.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]
Unbiased ResultsWe believe in providing patients with all the options.
Your Data Stays Your DataWe only share your information with the clinical trials you're trying to access.
Verified Trials OnlyAll of our trials are run by licensed doctors, researchers, and healthcare companies.
Back to top
Terms of Service·Privacy Policy·Cookies·Security