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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether combining high-dose, image-guided radiation therapy with immunotherapy can more effectively treat non-small cell lung cancer that has metastasized. The researchers aim to determine if this combination improves patient response to immunotherapy, which uses the body's immune system to combat cancer. The trial compares two groups: one receiving both radiation and immunotherapy, and another continuing with only their usual immunotherapy. Ideal participants have stage IV lung cancer or cancer that has spread after initial treatment and are already on immunotherapy. Participants should have a cancer spot that can be safely treated with radiation and recent imaging showing stable or slightly progressing cancer. As an unphased trial, this study provides patients a unique opportunity to contribute to innovative research that could enhance future cancer treatments.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining image-guided radiation therapy with immunotherapy is generally safe for treating non-small cell lung cancer (NSCLC). Studies have found this combination to be both safe and practical for patients. Some reports indicate that adding immunotherapy to radiation therapy does not significantly increase the risk of severe side effects.

In previous studies, patients tolerated this combination well, even with high doses of radiation. While some may experience common side effects like tiredness or skin reactions, these are usually manageable.

Always consult your healthcare provider about the potential risks and benefits before deciding to join a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the combination of image-guided radiation therapy and immunotherapy for lung cancer because it offers a potentially more precise and effective treatment approach. Unlike standard care that typically involves either radiation or immunotherapy alone, this combination uses advanced imaging techniques to target cancer cells with high precision while simultaneously enhancing the body's immune response to fight the cancer. This dual approach aims to maximize cancer cell destruction while minimizing damage to surrounding healthy tissue, potentially leading to better outcomes and fewer side effects.

What evidence suggests that this trial's treatments could be effective for lung cancer?

This trial will compare the effectiveness of two treatment approaches for lung cancer. One group of participants will receive a combination of image-guided radiation therapy and immunotherapy. Studies have shown that this combination can effectively treat lung cancer, with a median progression-free survival (PFS) of up to 42 months. This indicates that their cancer did not worsen for a longer time compared to other treatments, and the combination also significantly improved overall survival rates. Radiation therapy appears to enhance the immune system's ability to fight cancer when paired with immunotherapy. However, about 40% of patients experienced serious side effects, so considering the potential risks is important. Another group in this trial will receive immunotherapy alone, which is the standard of care. ^{2 3 4 6 7}

Who Is on the Research Team?

Michael Gensheimer

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Varian Medical Systems

Industry Sponsor

Trials

63

Recruited

3,700+

Dow R. Wilson

Varian Medical Systems

Chief Executive Officer since 2012

MBA from Dartmouth's Amos Tuck School of Business, BA from Brigham Young University

Dr. Deepak Khuntia

Varian Medical Systems

Chief Medical Officer since 2020

MD from the University of Cambridge, PhD from the University of Leicester

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11638397/

Efficacy and Mechanism of Combining Radiotherapy ... The study found median PFS lasting up to 42 months, and 40% of patients experienced grade 3 or greater treatment-related adverse events.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12273017/

Immunotherapy combined with radiotherapy in the ... The results of this study indicate that the combination of ICI and RT significantly prolongs the Progression-Free-Survival and Overall Survival ...

3. spandidos-publications.com spandidos-publications.com/10.3892/ol.2025.15215

Immunotherapy combined with radiotherapy for advanced ... The combined treatment of RT and ICIs appears to be an optimal tool to treat cancer as RT has notable synergistic antitumor effects with ...

4. nature.com nature.com/articles/s41392-022-01102-y

Radiotherapy combined with immunotherapy: the dawn of ... RT could be regarded as a trigger of systemic antitumor immune response, and with the help of IO can be used as a radical and systemic treatment.

5. sciencedirect.com sciencedirect.com/science/article/pii/S1525730423001535

Effect of Sequence of Radiotherapy Combined With ... Radiotherapy (RT) combined with immunotherapy is a novel and effective treatment strategy for lung cancer. However, the clinical application of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10040597/

Safety and efficacy of radiotherapy/chemoradiotherapy ... This study suggests that the addition of ICIs to RT/CRT for NSCLC patients may be both safe and feasible.

7. sciencedirect.com sciencedirect.com/science/article/pii/S0360301625045080

Low-dose Radiation Therapy Concurrent With ... These findings suggest that upfront LDRT concurrent with atezolizumab plus chemotherapy was effective and tolerable as first-line treatment for ES-SCLC.