Image-Guided Radiation + Immunotherapy for Lung Cancer

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Stanford University

Must be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: Untreated brain metastases, Pregnancy, others

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

Compensation: Varies

Number of Visits: 30

Duration: 2 weeks

44 Participants Needed

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. However, you must have been on immunotherapy for at least four weeks and are expected to continue it for at least three more months.

What data supports the effectiveness of this treatment for lung cancer?

Research suggests that combining radiation therapy with immunotherapy may improve survival rates in patients with advanced non-small-cell lung cancer (NSCLC) compared to using immunotherapy alone. Studies indicate that radiation can enhance the body's immune response to cancer, potentially leading to better outcomes. ^{1 2 3 4 5}

Is the combination of image-guided radiation therapy and immunotherapy safe for humans?

Research shows that combining immunotherapy with radiation therapy can be safe, but there is a risk of lung-related side effects, such as pneumonitis (lung inflammation). Monitoring patients closely for these side effects is important, especially in lung cancer treatments. ^{2 6 7 8 9}

How is the Image-Guided Radiation and Immunotherapy treatment for lung cancer different from other treatments?

This treatment is unique because it combines image-guided radiation therapy with immunotherapy, which can enhance the immune system's ability to fight cancer and improve tumor response. The synergy between these two approaches may lead to better survival rates and disease control compared to using either treatment alone. ^{2 4 10 11 12}

What is the purpose of this trial?

This phase II trial studies how well radical-dose image guided radiation therapy works in treating patients with non-small cell lung cancer that has spread to other places in the body who are undergoing immunotherapy. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving radical-dose image guided radiation therapy to patients with non-small cell lung cancer may help to improve response to immunotherapy anti-cancer treatment.

Research Team

Michael Gensheimer

Principal Investigator

Stanford University

Eligibility Criteria

This trial is for adults over 18 with stage IV non-small cell lung cancer or those whose earlier-stage lung cancer has spread. They must have been on standard immunotherapy for at least four weeks, be stable in terms of symptoms and performance status, and show a certain response to treatment on recent scans. Pregnant women or those not using contraception are excluded.

Inclusion Criteria

I can take care of myself and perform daily activities.

Evaluation by a Stanford medical oncologist must show:

The most recent imaging shows that there is a measurable disease according to a specific set of guidelines called RECIST 1.1.

Exclusion Criteria

I have brain metastases that are not being treated in this radiation therapy course.

Pregnancy or women of childbearing potential not willing/able to use contraception during protocol treatment

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients undergo radical-dose image guided radiation therapy daily for up to 10 days while continuing immunotherapy

2 weeks

Daily visits for radiation therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

Follow-up at 30 days and every 6 months thereafter

Treatment Details

Interventions

• Image-guided Radiation Therapy
• Immunotherapy (physician's choice for standard of care immunotherapy)
• Immunotherapy (standard of care)

Trial Overview The study is testing high-dose image guided radiation therapy in patients with metastatic non-small cell lung cancer who are also undergoing immunotherapy. The goal is to see if this combination improves the body's response to the immunotherapy treatment.

Participant Groups

Group I: Immunotherapy plus Image-guided Radiation Therapy Experimental Treatment 2 Interventions

Patients undergo radical-dose image guided radiation therapy daily for up to 10 days (within 2 weeks) while continuing their prior treatment with the treating physician's choice of regular medical care immunotherapy.

Group II: Immunotherapy Alone (Regular Medical Care) Active Control 1 Intervention

Patients who decline to undergo radiation therapy will continue their prior treatment with the treating physician's choice of regular medical care immunotherapy.

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Findings from Research

In a study of 44,498 patients with stage IV non-small-cell lung cancer (NSCLC), stereotactic radiotherapy (SRT) was associated with improved overall survival (OS), showing a hazard ratio of 0.78, indicating a significant benefit regardless of the type of systemic treatment used.

The combination of SRT and immunotherapy showed promising results, with patients receiving SRT having a median OS of 18.2 months compared to 14.3 months for those on chemotherapy, suggesting that SRT may enhance the effectiveness of immunotherapy and warrants further investigation in randomized trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overall survival according to immunotherapy and radiation treatment for metastatic non-small-cell lung cancer: a National Cancer Database analysis. Foster, CC., Sher, DJ., Rusthoven, CG., et al.[2020]

Combining thoracic radio(chemo)therapy with immune checkpoint inhibitors in non-small cell lung cancer (NSCLC) poses a risk of overlapping pulmonary toxicity, making careful patient selection and monitoring essential for optimizing treatment outcomes.

Future strategies should focus on identifying patients who can benefit from this combination therapy while also assessing those at higher risk for severe side effects, using clinical evaluations and biomarkers to guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined radiation- and immune checkpoint-inhibitor-induced pneumonitis - The challenge to predict and detect overlapping immune-related adverse effects from evolving laboratory biomarkers and clinical imaging. Guberina, N., Wirsdörfer, F., Stuschke, M., et al.[2023]

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 study of 60 patients receiving combined immunotherapy and thoracic radiation therapy (iRT), no patients experienced severe grade ≥4 toxicities, indicating a favorable safety profile for this treatment approach.

While some patients did experience grade 3 toxicities, particularly pulmonary and hematologic issues, the overall short-term safety of iRT suggests it can be administered without significant risk of severe adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Combined Immunotherapy and Thoracic Radiation Therapy: Analysis of 3 Single-Institutional Phase I/II Trials. Verma, V., Cushman, TR., Selek, U., et al.[2022]

In a study of 96 lung cancer patients who received thoracic radiotherapy (TRT) after PD-(L)1 inhibitor treatment, nearly 49% developed symptomatic treatment-related pneumonitis, indicating a significant safety concern with this treatment sequence.

Independent risk factors for developing pneumonitis included pulmonary emphysema and lung V20 exposure, highlighting the need for careful patient selection and monitoring when using TRT after PD-(L)1 inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of thoracic radiotherapy after PD-(L)1 inhibitor treatment in patients with lung cancer. Chen, Y., Liu, X., Huang, Z., et al.[2022]

Combining radiotherapy with immunotherapies appears to be safe, as it does not lead to increased toxicity, even at definitive doses of radiotherapy.

Recent clinical trials, like the PACIFIC trial, have shown promising results regarding the safety and efficacy of these combinations, suggesting potential benefits such as abscopal effects, where treatment at one site affects distant tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation Therapy and Immune Modulation. Leeman, JE., Schoenfeld, JD.[2020]

Immunotherapy, particularly in combination with radiotherapy, is a promising treatment approach for non-small cell lung cancer, showing potential for improved tumor response and patient survival.

The review discusses the biochemical and molecular mechanisms behind the synergy of these treatments and highlights ongoing clinical trials aimed at optimizing their combination to maximize efficacy while minimizing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New challenges in the combination of radiotherapy and immunotherapy in non-small cell lung cancer. Luna, J., Zafra, J., Areses Manrique, MC., et al.[2023]

Recent advancements in immunotherapy for non-small cell lung cancer (NSCLC), including drugs like nivolumab and pembrolizumab, have shown significant efficacy in treating metastatic cases and unresectable stage III NSCLC.

Combining radiation therapy (RT) with immunotherapy has demonstrated potential to enhance tumor immunity, leading to ongoing trials that aim to optimize treatment strategies for NSCLC, emphasizing the importance of careful patient selection for better clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy and Immunotherapy Combinations for Lung Cancer. Agrawal, V., Benjamin, KT., Ko, EC.[2021]

References

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

Overall survival according to immunotherapy and radiation treatment for metastatic non-small-cell lung cancer: a National Cancer Database analysis. [2020]

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

Combined radiation- and immune checkpoint-inhibitor-induced pneumonitis - The challenge to predict and detect overlapping immune-related adverse effects from evolving laboratory biomarkers and clinical imaging. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Radiotherapy improves the outcomes of immunotherapy with Sintilimab in non-small-cell lung cancer: A real-world analysis. [2022]

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

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

5. Egypt pubmed.ncbi.nlm.nih.gov

Assessing Potential Factors Influencing the Efficacy of Immune Checkpoint Inhibitors with Radiation in Advanced Non-Small-Cell Lung Cancer Patients: A Systematic Review and Meta-Analysis. [2023]

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

Safety of Combined Immunotherapy and Thoracic Radiation Therapy: Analysis of 3 Single-Institutional Phase I/II Trials. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

[Adverse effects of immunotherapy : Clinical aspects, radiological and nuclear medicine results]. [2019]

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

Safety of thoracic radiotherapy after PD-(L)1 inhibitor treatment in patients with lung cancer. [2022]

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

Radiation Therapy and Immune Modulation. [2020]

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

New challenges in the combination of radiotherapy and immunotherapy in non-small cell lung cancer. [2023]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Radiotherapy and Immunotherapy in Lung Cancer. [2023]

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

Radiotherapy and Immunotherapy Combinations for Lung Cancer. [2021]