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

Trial Summary

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.

What data supports the effectiveness of the treatment Grid Radiation Therapy + Immunotherapy for Lung Cancer?

Research suggests that combining spatially fractionated radiation therapy (SFRT) with immunotherapy can enhance the body's immune response against tumors, potentially leading to better outcomes. Studies in mice have shown that this combination can delay tumor growth and trigger immune responses even in areas not directly treated, indicating a promising approach for treating cancer. ^{1 2 3 4 5}

Is Grid Radiation Therapy combined with Immunotherapy safe for humans?

Grid Radiation Therapy, also known as Spatially Fractionated Radiation Therapy (SFRT), has been used safely in clinical settings for treating large tumors, with reports of no lasting side effects in some cases. When combined with immunotherapy, it has shown promising results without significant safety concerns in patients with conditions like melanoma and soft tissue sarcomas. ^{3 5 6 7 8}

How does Grid Radiation Therapy combined with Immunotherapy differ from other treatments for lung cancer?

Grid Radiation Therapy is unique because it uses a spatially fractionated approach, delivering high doses of radiation in a non-uniform pattern, which can enhance the immune response when combined with immunotherapy. This method may improve treatment outcomes for large, bulky tumors by promoting both local and systemic anti-tumor immune responses, potentially offering benefits over conventional uniform-dose radiotherapy. ^{1 2 4 5 9}

What is the purpose of this trial?

This phase II trial tests the safety and effectiveness of the combination of grid radiation therapy and standard of care (SOC) immunotherapy in treating patients with stage IV non-small lung cancer (NSCLC). Conventional radiation therapy treatments typically deliver the same radiation dose to the entire tumor. Spatially fractionated radiation therapy or grid therapy is approved and a technique which permits the delivery of high doses of radiation to small regions of the tumor which can lead to enhanced tumor cell killing. Grid therapy has been shown to produce dramatic relief of severe symptoms, significant tumor regression (decrease in the size of a tumor), and above average local control rates often exceeding those expected with conventionally delivered radiation treatments, all with minimal associated toxicity. Immunotherapy has become combined into treating patients, which has led improvements in survival and quality of life. Immunotherapy is now the cornerstone of SOC therapy for stage IV NSCLC. Grid radiation therapy combined with immunotherapy may be safe and effective in treating patients with stage IV NSCLC.

Research Team

Dawn Owen, M.D.

Principal Investigator

Mayo Clinic in Rochester

Eligibility Criteria

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.

My kidney function is within the required range for the study.

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

Exclusion Criteria

Hypersensitivity to immunotherapy

I have received an organ transplant from another person.

History of active primary immunodeficiency

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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 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]

References

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

Early clinical results of proton spatially fractionated GRID radiation therapy (SFGRT). [2022]

2. England pubmed.ncbi.nlm.nih.gov

Effective spatially fractionated GRID radiation treatment planning for a passive grid block. [2022]

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

Immune Priming with Spatially Fractionated Radiation Therapy. [2023]

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

Evidence for Early Stage Anti-Tumor Immunity Elicited by Spatially Fractionated Radiotherapy-Immunotherapy Combinations. [2023]

5. United States 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. [2021]

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

High-Dose Radiation as a Dramatic, Immunological Primer in Locally Advanced Melanoma. [2020]

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

2D mapping of radiation dose and clonogenic survival for accurate assessment ofin vitroX-ray GRID irradiation effects. [2023]

8. United States 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. [2021]

9. England pubmed.ncbi.nlm.nih.gov

An investigation of kV mini-GRID spatially fractionated radiation therapy: dosimetry and preclinical trial. [2023]