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

6 Participants Needed

Trial Summary

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 data supports the effectiveness of the treatment IRE + Radiation Therapy for Metastatic Lung Cancer?

Radiotherapy is a key treatment for non-small cell lung cancer, with techniques like intensity-modulated radiotherapy (IMRT) and stereotactic body radiotherapy (SBRT) showing promise in targeting tumors more precisely. Additionally, image-guided brachytherapy has been effective in treating isolated lung tumors, suggesting that combining these advanced radiotherapy techniques with IRE could potentially enhance treatment outcomes for metastatic lung cancer. ^{1 2 3 4 5}

Is the combination of IRE and radiation therapy generally safe for humans?

The research articles focus on the safety of combining radiation therapy with immune checkpoint inhibitors, highlighting immune-related adverse events (irAEs) as a concern. While these studies do not directly address IRE combined with radiation therapy, they suggest that combining radiation with other treatments can lead to specific side effects, which need careful monitoring and management. ^{6 7 8 9 10}

How is the IRE + Radiation Therapy treatment for metastatic lung cancer different from other treatments?

The IRE + Radiation Therapy treatment is unique because it combines irreversible electroporation (IRE), a technique that uses electrical pulses to destroy cancer cells, with advanced forms of radiation therapy. This combination aims to enhance the precision and effectiveness of targeting metastatic lung cancer, potentially offering a novel approach compared to traditional treatments that often rely solely on chemotherapy or standard radiotherapy. ^{1 3 4 11 12}

What is the purpose of this trial?

This is a phase 0, pilot prospective study to determine the feasibility of combined irreversible electroporation (IRE) and radiation therapy in subjects with lung tumors with metastatic cancer of any histology. These are subjects who have advanced disease (stage IV) or previously treated disease that has become progressive, recurrent, or metastatic.

Research Team

Jeremy Harris

Principal Investigator

Chao Family Comprehensive Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

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

Repeated iodine-125 seed implantations combined with external beam radiotherapy for the treatment of locally recurrent or metastatic stage III/IV non-small cell lung cancer: a retrospective study. [2022]

2. China 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. [2023]

3. France pubmed.ncbi.nlm.nih.gov

[Radiotherapy for non-small cell lung cancer]. [2009]

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

Computed tomography-guided interstitial high-dose-rate brachytherapy in the local treatment of primary and secondary intrathoracic malignancies. [2022]

5. France pubmed.ncbi.nlm.nih.gov

[Stage IIIB non-small cell lung cancer. Optimization of radiotherapy in lung cancer: some interesting questions to be solved]. [2007]

6. United States 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. [2022]

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

Immune-Related Adverse Events in Cancer Patients Treated With Immune Checkpoint Inhibitors. [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

[Management of immune-related adverse events (irAEs) - what needs to be respected?] [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of immune checkpoint inhibitors in combination with palliative radiotherapy in advanced melanoma: A systematic review. [2021]

10. Denmark pubmed.ncbi.nlm.nih.gov

[Immunotherapy is cancer treatment with a novel side-effect profile]. [2019]

11. China pubmed.ncbi.nlm.nih.gov

[Therapeutic Effect of CT-guided ¹²⁵I Seed Implantation on Advanced Lung Cancer and Pulmonary Metastatic Carcinoma]. [2021]

12. China pubmed.ncbi.nlm.nih.gov

Current landscape of palliative radiotherapy for non-small-cell lung cancer. [2020]