IRE + Radiation Therapy for Metastatic Lung Cancer

Overseen By University of California Irvine Medical

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of California, Irvine

Must not be taking: Investigational agents

Disqualifiers: Pneumonitis, Cardiac arrhythmias, Epilepsy, others

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

Compensation: Varies

Number of Visits: 2

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the use of two treatments, irreversible electroporation (IRE) ablation and radiation therapy, to determine their combined effectiveness in treating lung tumors that have spread from other cancers. It targets individuals with advanced stage IV cancer who have tried other treatments but still experience growing or returning tumors. Suitable participants should have a lung tumor untreated by radiation and easily measurable on a CT scan. This trial excludes individuals with certain health issues, such as a history of severe lung inflammation or heart problems. As an Early Phase 1 trial, the research focuses on understanding how these treatments work in people, offering participants the opportunity to be among the first to receive this innovative combination therapy.

Will I have to stop taking my current medications?

You will need to stop your current systemic therapy while receiving IRE and radiation therapy, but you can restart it after completing the radiation therapy. The trial does not specify a washout period before starting IRE.

What prior data suggests that this combination of irreversible electroporation and radiation therapy is safe for metastatic lung cancer?

A previous study found irreversible electroporation (IRE) to be safe, even near sensitive areas like bile ducts and major blood vessels. However, 24.1% of patients reported side effects within 90 days of treatment.

Research shows that radiation therapy is effective with few serious side effects. Specifically, stereotactic body radiation therapy (SBRT) has successfully controlled lung tumors with manageable side effects.

Overall, research supports the safety of both treatments, though some side effects may still occur. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using irreversible electroporation (IRE) and radiation therapy for metastatic lung cancer because this approach offers a unique combination of treatments. Unlike traditional treatments like chemotherapy or standard radiation therapy, IRE uses electrical pulses to create tiny holes in cancer cell membranes, causing them to die without affecting the surrounding healthy tissue. This precision can lead to fewer side effects and potentially more effective targeting of the cancer cells. Additionally, when followed by moderate-dose, single-fraction radiation therapy, the treatment may enhance the overall effectiveness by further damaging the cancer cells left behind, which could lead to better outcomes for patients.

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

This trial will evaluate the combination of irreversible electroporation (IRE) ablation and radiation therapy for metastatic lung cancer. Research has shown that IRE can destroy cancer cells without heat, but results have been mixed. Some studies indicate that IRE has not been very effective for lung cancer or cancer that has spread to the lungs, possibly due to tumor variability.

In contrast, radiation therapy, specifically stereotactic body radiation therapy (SBRT), has shown more promising results. Studies have found that SBRT can control up to 80% of lung tumors for two years and is associated with a survival rate of about 72% after two years. This trial aims to combine the strengths of both methods. ^{1 4 5 6 7}

Who Is on the Research Team?

Jeremy Harris

Principal Investigator

Chao Family Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with stage IV or recurrent metastatic cancer that has spread to the lungs. They must have a life expectancy of at least 3 months, be in fair physical condition (ECOG ≤2), and have proper organ function. Participants can't join if they're recovering from side effects of previous cancer treatments, have certain heart conditions, uncontrolled illnesses, are pregnant, or could receive curative treatment elsewhere.

Inclusion Criteria

I can take care of myself but might not be able to do heavy physical work.

My cancer has spread, and I have a tumor in my lung.

I have never needed steroids for non-infectious lung inflammation.

Exclusion Criteria

I have another cancer that is getting worse or needs treatment.

You have not yet healed from side effects caused by previous cancer treatments.

My target lesion has been treated with radiation before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive IRE ablation on day 1 and moderate-dose, single-fraction radiation therapy between day 8 and day 15

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including pulmonary function and quality of life assessments

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Irreversible electroporation (IRE) ablation
• Radiation Therapy

Trial Overview The study is testing a new approach combining irreversible electroporation (IRE) ablation and radiation therapy on lung tumors in patients with advanced cancer. It's an early-stage trial to see if this combo is feasible and how well it works when other treatments haven't helped.

How Is the Trial Designed?

Group I: IRE ablation and radiation therapy Experimental Treatment 2 Interventions

Patients will be treated with IRE ablation directed at the target lesion on day 1. Moderate-dose, single-fraction radiation therapy will be delivered to the target lesion on day 8 to day 15.

Who Is Running the Clinical Trial?

University of California, Irvine

Lead Sponsor

Trials

580

Recruited

4,943,000+

Published Research Related to This Trial

In a study of 133 patients with metastatic cancers receiving immune checkpoint inhibitors and radiation, 34.6% experienced immune-related adverse events (ir-AEs), with higher rates observed in those receiving both CTLA-4 and PD-1 inhibitors (71% vs 29%).

The combination of palliative radiation and immune checkpoint inhibitors was generally well tolerated, with most ir-AEs being mild, suggesting that this treatment approach can be safely integrated in clinical practice for patients needing both therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter Evaluation of the Tolerability of Combined Treatment With PD-1 and CTLA-4 Immune Checkpoint Inhibitors and Palliative Radiation Therapy. Bang, A., Wilhite, TJ., Pike, LRG., et al.[2022]

Combining palliative radiotherapy (pRT) with immune checkpoint inhibitors (ICI) in melanoma treatment significantly improved objective response rates, complete response rates, and one-year local control, indicating enhanced efficacy of the treatment.

The combination treatment did not lead to a significant increase in adverse events or immune-related adverse events compared to ICI alone, suggesting that it is a safe option for patients with advanced melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of immune checkpoint inhibitors in combination with palliative radiotherapy in advanced melanoma: A systematic review. Ben Shimol, J., Guzman-Prado, Y., Karlinskaya, M., et al.[2021]

Radiotherapy is essential for treating advanced non-small-cell lung cancer (NSCLC), but clinical practices vary widely despite established guidelines.

The introduction of stereotactic ablative radiotherapy (SABR) and immunotherapy has changed treatment strategies, highlighting the need for updated approaches in palliative thoracic radiotherapy for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current landscape of palliative radiotherapy for non-small-cell lung cancer. Jumeau, R., Vilotte, F., Durham, AD., et al.[2020]

In a study of 120 stage IV non-small cell lung cancer patients treated with immunotherapy, the addition of external beam radiation therapy (EBRT) or radioactive particle implantation (RPI) did not significantly improve overall survival compared to immunotherapy alone, with median survival times of 9 months for IT alone and 10 months for IT with EBRT.

Subgroup analyses indicated that patients receiving RPI had poorer prognoses, particularly in males and those with specific metastases, suggesting that while RT may not enhance survival overall, certain patient characteristics could influence outcomes negatively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy with radiotherapy fails to improve prognosis of patients with stage IV non-small cell lung cancer: a retrospective cohort analysis of the THUNDER-2 study. Liu, L., Yuan, M., Ding, Z., et al.[2023]

Concurrent chemoradiation is the standard treatment for locally advanced unresectable non-small-cell lung cancer, highlighting its efficacy as a major therapeutic option.

New radiotherapy techniques, such as respiratory gating and intensity-modulated radiotherapy, are being developed to improve treatment precision, while stereotactic and proton-beam therapies may offer better options for early-stage tumors in non-operable patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Radiotherapy for non-small cell lung cancer]. Girard, N., Mornex, F.[2009]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3560719/

Irreversible electroporation of lung neoplasm: A case series IRE has shown promise as a technique for non-thermal ablation of tumors in several organs. There has been more literature concerning the liver than any other ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2211568417301973

Irreversible electroporation and thermal ablation of tumors ... Here, established thermal ablation techniques are compared with irreversible electroporation for treatment of tumors in the lung, liver, kidney and bone.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8558078/

Lung Ablation with Irreversible Electroporation Promotes ... Preliminary evaluation of IRE in the lung yielded unsatisfactory outcomes, dampening further utilization in the clinic. This might be due to heterogeneity in ...

4. journals.lww.com journals.lww.com/otm/fulltext/2025/08000/irreversible_electroporation__current_research.3.aspx

Irreversible electroporation: current research status and... A recent clinical trial in patients with lung cancer showed that IRE was ineffective in treating primary lung cancer or malignant lung metastases.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e16301

Effectiveness and safety of irreversible electroporation ... There were 21 (24.1%) patients who developed AEs related to IRE treatment during the 90-day post-procedure period (9 patients had AEs that were ...

6. jvir.org jvir.org/article/S1051-0443(13)00086-9/fulltext

Safety of irreversible electroporation (IRE) treatment for ... IRE, even when preformed in close proximity to bile ducts, major vessels, bladder, rectum, and nerves, has an acceptable safety profile in our experience.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1051044313000869

Safety of irreversible electroporation (IRE) treatment for ... IRE, even when preformed in close proximity to bile ducts, major vessels, bladder, rectum, and nerves, has an acceptable safety profile in our experience.