Grid Radiation Therapy + Immunotherapy for Lung Cancer

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must be taking: Immunotherapy

Must not be taking: Systemic steroids

Disqualifiers: Autoimmune disease, Hepatitis, Tuberculosis, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 1 week

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new combination of treatments for individuals with stage IV non-small cell lung cancer. It combines grid therapy, a special radiation therapy that targets parts of the tumor with high doses, with standard immunotherapy, a biological therapy that helps the immune system fight cancer. The goal is to determine if this combination can reduce tumor size and improve symptoms more effectively than standard treatments. Individuals with stage IV non-small cell lung cancer that hasn't improved with initial treatments might be suitable candidates. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on systemic steroids or immunosuppressive agents for an active autoimmune disease, you may not be eligible to participate.

Is there any evidence suggesting that the combination of grid radiation therapy and immunotherapy is likely to be safe for humans?

Research has shown that grid radiation therapy, when combined with immunotherapy, might safely treat stage IV non-small cell lung cancer. Grid therapy targets high doses of radiation on small tumor areas and has successfully shrunk tumors and controlled cancer growth with few side effects.

Studies have found that this radiation therapy can significantly relieve severe symptoms and help control the tumor locally. Importantly, it usually has low toxicity, causing few harmful side effects.

Immunotherapy is already a common treatment for stage IV lung cancer, known to help many patients live longer and improve their quality of life. Together, these treatments show promise for effectively managing advanced lung cancer while being generally well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard care options for lung cancer, such as traditional radiation therapy and chemotherapy, Grid Radiation Therapy offers a unique approach by targeting tumors with a high-dose radiation grid pattern. This method allows for more precise targeting of cancer cells while sparing surrounding healthy tissue, potentially reducing side effects. Additionally, when combined with immunotherapy, this approach might enhance the body's immune response against the cancer, offering a promising synergistic effect. Researchers are excited about this combination because it could provide faster results and improved outcomes for patients with lung cancer.

What evidence suggests that grid radiation therapy combined with immunotherapy might be an effective treatment for stage IV NSCLC?

This trial will evaluate the combination of grid radiation therapy and standard immunotherapy for stage IV non-small cell lung cancer (NSCLC). Studies have shown that grid radiation therapy, which targets high doses to specific parts of a tumor, can lead to significant tumor shrinkage and better tumor control compared to regular radiation. Research indicates that combining grid therapy with standard immunotherapy enhances treatment effectiveness for advanced lung cancer. Immunotherapy, already crucial in treating advanced lung cancer, helps the immune system fight cancer cells more effectively. Grid therapy has also been associated with significant relief from severe symptoms and only minor side effects. These promising results suggest that this combination could be a strong treatment option for patients with advanced lung cancer. ^{1 4 5 6 7}

Who Is on the Research Team?

Dawn Owen, M.D.

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

This trial is for patients with stage IV non-small cell lung cancer. Participants should be eligible for standard of care immunotherapy and have not received grid radiation therapy before. Specific eligibility will depend on additional criteria set by the study.

Inclusion Criteria

My stage IV lung cancer is getting worse despite first-line immunotherapy.

Negative pregnancy test done ≤ 7 days prior to grid therapy, for females of childbearing potential only

Willing to return to Mayo Clinic for follow-up (during the Active Monitoring Phase of the study)

Exclusion Criteria

Hypersensitivity to immunotherapy

History of active primary immunodeficiency

I have received an organ transplant from another person.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients undergo grid radiation therapy over a single fraction on day 1 and palliative radiation therapy over 5 fractions on days 2 and -1 post-grid, along with SOC immunotherapy and CT scans as needed.

1 week

Multiple visits for radiation therapy and ongoing immunotherapy

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits at 30 days, then every 8-12 weeks, and every 3 months up to 5 years.

Up to 5 years

Regular follow-up visits every 8-12 weeks and every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Grid Radiation Therapy
• Immunotherapy

Trial Overview

The trial is testing if combining grid radiation therapy, which targets small regions of a tumor with high doses of radiation, with standard immunotherapy treatments can improve outcomes in stage IV NSCLC patients.

How Is the Trial Designed?

Group I: Treatment (grid radiation therapy) Experimental Treatment 5 Interventions

Patients undergo grid radiation therapy over a single fraction on day 1 and palliative radiation therapy over 5 fractions on days 2 and -1 post-grid in the absence of disease progression or unacceptable toxicity. Patients also receive SOC immunotherapy and undergo CT at the discretion of the physician and undergo blood sample collection throughout the study.

Grid Radiation Therapy is already approved in United States, European Union for the following indications:

Approved in United States as Grid Therapy for:

• Non-Small Cell Lung Cancer (NSCLC)
• Bulky radioresistant tumors

Approved in European Union as Spatially Fractionated Radiation Therapy for:

• Non-Small Cell Lung Cancer (NSCLC)
• Large unresectable tumors

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

The study developed novel mini-GRID radiation therapy methods that achieved high peak-to-valley ratios, indicating a potential for more targeted treatment while sparing healthy tissue, with ratios significantly higher than those reported for conventional methods.

In a pre-clinical mouse study, both GRID therapy and hemi-irradiation effectively delayed tumor growth compared to controls, but neither was as effective as traditional whole-tumor irradiation, suggesting that while promising, GRID therapy may need to be combined with other treatments to enhance its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An investigation of kV mini-GRID spatially fractionated radiation therapy: dosimetry and preclinical trial. Johnson, TR., Bassil, AM., Williams, NT., et al.[2023]

Spatially fractionated radiation therapy (SFRT) can enhance the immune response against tumors by increasing immune cell infiltration and activating T cells, potentially improving the effectiveness of immunotherapy (IT).

Combining SFRT with IT may help overcome immune resistance in cancer treatment, making it a promising strategy to boost the overall efficacy of cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Priming with Spatially Fractionated Radiation Therapy. Lukas, L., Zhang, H., Cheng, K., et al.[2023]

Proton spatially fractionated GRID radiation (SFGRT) was successfully used to treat 10 patients with large tumors that could not be treated with photon GRID due to critical organ proximity, showing an 80% rate of tumor regression or local symptom improvement.

The treatment was well-tolerated, with 50% of patients experiencing only mild acute side effects, indicating that proton SFGRT is a feasible and effective alternative for patients who cannot receive photon-based treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early clinical results of proton spatially fractionated GRID radiation therapy (SFGRT). Mohiuddin, M., Lynch, C., Gao, M., et al.[2022]

The study successfully implemented a grid block for spatially fractionated grid radiation therapy (SFGRT), demonstrating that it can effectively treat bulky tumors with a significant reduction in treatment time compared to traditional methods, improving patient throughput.

Dosimetric measurements showed that the grid block technique has clinically acceptable accuracy, with discrepancies in dose calculations being minimal (less than 4% in the build-up region and less than 2% at deeper levels), supporting its safe and effective use in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective spatially fractionated GRID radiation treatment planning for a passive grid block. Nobah, A., Mohiuddin, M., Devic, S., et al.[2022]

In a study using an immunocompetent mouse model with triple negative breast tumors, spatial fractionation of radiation (GRID) combined with immune checkpoint inhibitors (PD1 and CTLA-4) significantly enhanced anti-tumor immune responses, leading to tumor growth delay not only in the treated tumor but also in distant (abscopal) tumors.

The GRID treatment resulted in increased infiltration of immune cells and systemic immune activation, suggesting that this approach could improve the effectiveness of cancer therapies by promoting immune responses beyond the primary tumor site.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence for Early Stage Anti-Tumor Immunity Elicited by Spatially Fractionated Radiotherapy-Immunotherapy Combinations. Johnsrud, AJ., Jenkins, SV., Jamshidi-Parsian, A., et al.[2023]

Spatially fractionated radiotherapy (GRID) has shown promising results in treating large, high-risk tumors, particularly soft tissue and osteosarcomas, by allowing for safe dose escalation and enhancing the effects of conventional radiotherapy.

In a study of 26 patients, incorporating a single fraction of GRID radiation before standard treatment resulted in excellent pathologic responses and demonstrated an apparent safety profile, suggesting its potential as an effective treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spatially Fractionated Radiotherapy (GRID) Prior to Standard Neoadjuvant Conventionally Fractionated Radiotherapy for Bulky, High-Risk Soft Tissue and Osteosarcomas: Feasibility, Safety, and Promising Pathologic Response Rates. Snider, JW., Molitoris, J., Shyu, S., et al.[2021]

The study developed a framework to link local radiation doses to the survival of A549 lung cancer cells, showing that spatially fractionated radiation therapy (GRID) results in reduced cell survival in peak dose regions compared to traditional open field irradiation.

Using advanced dosimetry techniques, the research found that the dose distribution from GRID irradiation was consistent, with a peak-to-valley dose ratio of about 5, indicating a significant difference in the effectiveness of radiation delivery in different areas of the treatment field.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

2D mapping of radiation dose and clonogenic survival for accurate assessment ofin vitroX-ray GRID irradiation effects. Arous, D., Lie, JL., Håland, BV., et al.[2023]

A 53-year-old male with metastatic melanoma showed complete resolution of a large neck mass after receiving a single high-dose GRID radiation therapy (20 Gy) combined with pembrolizumab, demonstrating the potential efficacy of this treatment approach.

The case suggests that high-dose GRID radiation can enhance the immune response to immunotherapy, as evidenced by the patient's rapid and durable results without lasting side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Dose Radiation as a Dramatic, Immunological Primer in Locally Advanced Melanoma. Mohiuddin, M., Park, H., Hallmeyer, S., et al.[2020]

Spatially fractionated radiation therapy (SFRT), such as GRID radiation therapy, shows promise in improving treatment responses for bulky primary and metastatic cancers by using a highly heterogeneous dose distribution, which allows for higher prescription doses than conventional radiotherapy.

The Physics Working Group of the Radiosurgery Society has developed consensus recommendations to standardize GRID therapy practices, which is crucial for enhancing clinical outcomes and facilitating rigorous clinical trials in this innovative treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photon GRID Radiation Therapy: A Physics and Dosimetry White Paper from the Radiosurgery Society (RSS) GRID/LATTICE, Microbeam and FLASH Radiotherapy Working Group. Zhang, H., Wu, X., Zhang, X., et al.[2021]

Citations

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Spatially fractionated radiation therapy: History, present and ...

For example, the results with SBRT/stereotactic ablative radiotherapy [SABR] in early-stage lung cancer patients have shown local control rates up to 86% [15], ...

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redjournal.org

redjournal.org/article/S0360-3016(25)06150-4/abstract

Grid Spatially Fractionated Radiation Therapy for Bulky ...

We retrospectively reviewed patients with locally advanced or metastatic bulky tumors treated with grid-RT from December 2013 to June 2022.

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This review focuses on both preclinical and clinical studies that use a combination of radiotherapy and ICI therapy in cancer.

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Modeling the impact of intercellular signaling on dose ...

Spatially fractionated radiation therapy (SFRT) delivers heterogeneous dose distributions to enhance tumor control while reducing normal ...

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redjournal.org

redjournal.org/article/S0360-3016(25)00383-9/fulltext

Reported Early Clinical Outcomes of Forward-Planned ...

Conventionally fractionated radiation therapy for large, bulky (≥8 cm), unresectable tumors has been hampered by radiation-induced morbidity ...

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sciencedirect.com

sciencedirect.com/science/article/pii/S2452109423001367

Practice Patterns of Spatially Fractionated Radiation Therapy

In curative-intent treatment, concurrent chemotherapy and immunotherapy were found acceptable by 54.5% and 28.6%, respectively. Use of SFRT dosimetric ...