Local Ablative Therapy for Non-Small Cell Lung Cancer

Recruiting at 10 trial locations

Overseen By Bob Li, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Platinum-doublet chemotherapy, ICI

Must not be taking: Targeted agents

Disqualifiers: CNS-only disease, Serious comorbidities, 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 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

90 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to see whether receiving local ablative therapy (LAT) when minimal residual disease/MRD levels are rising can reduce MRD levels and control metastatic non-small cell lung cancer/NSCLC longer compared to systemic therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should have received at least two cycles of first-line systemic therapy and remain on it, suggesting that you may continue your current treatment.

What data supports the effectiveness of this treatment for non-small cell lung cancer?

Research shows that stereotactic body radiation therapy (SBRT), also known as stereotactic ablative radiotherapy (SABR), is a safe and effective treatment for early-stage non-small cell lung cancer (NSCLC), especially for patients who cannot undergo surgery. It offers good local control and outcomes similar to surgery, with low toxicity for tumors located away from sensitive structures. ^{1 2 3 4 5}

Is local ablative therapy for non-small cell lung cancer safe?

Local ablative therapy, also known as stereotactic ablative radiotherapy (SABR), is generally safe for treating lung tumors, especially when they are small and not near critical structures. However, there is a risk of serious complications if the tumors are close to important areas like the bronchial tree or mediastinum (the area between the lungs). ^{4 6 7 8 9}

How is the treatment for non-small cell lung cancer different from other treatments?

Local ablative therapy, also known as stereotactic ablative radiotherapy (SABR) or stereotactic body radiation therapy (SBRT), is unique because it delivers high doses of radiation with precision over a few sessions, making it a noninvasive option for patients who cannot undergo surgery. It is particularly effective for early-stage non-small cell lung cancer and offers similar local control to surgery with relatively low toxicity. ^{3 4 10 11 12}

Research Team

Daniel Gomez

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults over 18 with Stage IV NSCLC who've had up to four cycles of standard therapy, have measurable disease but not more than ten lesions, and no active cancers in the last year. They must be able to undergo radiotherapy, not be pregnant or breastfeeding, and have adequate organ function.

Inclusion Criteria

I've had up to 4 rounds of initial cancer treatment.

I don't have serious health issues that would prevent me from getting radiotherapy or ablation.

I had imaging tests done within 4 weeks of my blood test for cancer DNA.

Exclusion Criteria

I have health issues that prevent me from receiving radiation or ablation treatments.

I cannot have stereotactic radiotherapy due to physical limitations.

I haven't had any cancer, except for skin cancer, in the last 5 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part I

Participants with metastatic NSCLC receive Local Ablative Therapy (LAT) to determine if ablation to all sites of disease leads to acceptable rates of mean VAF reduction.

6 months

Treatment Part II

Participants are randomized to either continuation of systemic therapy or ablation to all sites of disease, with a primary endpoint of progression-free survival.

3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, with imaging obtained every 3 months.

6 months

Treatment Details

Interventions

• Blood collection to assess for ctDNA
• Local ablative therapy

Trial Overview The study tests if local ablative therapy (LAT) can lower minimal residual disease levels and control metastatic NSCLC better than systemic therapy when MRD levels are rising. Blood will also be collected to check for circulating tumor DNA.

Participant Groups

Group I: Part II - ablation to all sites of disease (experimental arm) Experimental Treatment 2 Interventions

If the appropriate criteria are met in part I,, in part II 60 patients with NR-VAF but without radiographic progression of disease will be randomized to one of two arms: continuation of systemic therapy (standard of care) vs. ablation to all sites of disease (experimental arm), with a primary endpoint of progression free survival.

Group II: Part I Experimental Treatment 2 Interventions

In part I, 33 patients with metastatic NSCLC with: a) NR-VAF but b) without radiographic progression of disease, will be treated with LAT to determine if ablation to all sites of disease leads to acceptable rates of mean VAF reduction, thus indicating a discernible molecular/clinical response in this subgroup of patients with metastatic disease.

Group III: Part II - standard of care Active Control 1 Intervention

If the appropriate criteria are met in part I,, in part II 60 patients with NR-VAF but without radiographic progression of disease will be randomized to one of two arms: continuation of systemic therapy (standard of care) vs. ablation to all sites of disease (experimental arm), with a primary endpoint of progression free survival.

Local ablative therapy is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Local ablative therapy for:

• Non-small cell lung cancer (NSCLC)
• Oligometastatic NSCLC

Approved in United States as Local ablative therapy for:

• Non-small cell lung cancer (NSCLC)
• Oligometastatic NSCLC

Approved in Canada as Local ablative therapy for:

• Non-small cell lung cancer (NSCLC)
• Oligometastatic NSCLC

Approved in Japan as Local ablative therapy for:

• Non-small cell lung cancer (NSCLC)
• Oligometastatic NSCLC

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Findings from Research

Hypofractionated stereotactic body radiation therapy (SBRT) for early-stage nonsmall cell lung carcinoma was found to be safe and effective, with no significant toxicity reported in a study of nine patients over an 18-month follow-up period.

Using an active breath coordinator (ABC) during treatment resulted in smaller planning target volumes and less lung exposure to radiation compared to free breathing, suggesting that ABC may enhance treatment precision without increasing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy for early-stage primary lung cancer, is an active breath coordinator necessary? An audit from a tertiary cancer care center. Madhavan, R., Renilmon, PS., Nair, HM., et al.[2018]

In a study of 160 patients with early-stage non-small cell lung cancer (NSCLC), stereotactic body radiation therapy (SBRT) achieved a higher 3-year local control rate of 87.7% compared to 71.7% for accelerated hypofractionated radiation therapy (AHRT).

Both treatment methods showed similar overall survival rates and limited toxicity, with no severe (G3 or G4) side effects reported, indicating that both SBRT and AHRT are safe and effective options for treating early-stage NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of accelerated hypofractionation and stereotactic body radiotherapy for Stage 1 and node negative Stage 2 non-small cell lung cancer (NSCLC). Lucas, JT., Kuremsky, JG., Soike, M., et al.[2022]

Stereotactic ablative radiotherapy (SABR) is an effective treatment for early-stage non-small cell lung cancers (NSCLCs) that are medically inoperable, providing local control and toxicity levels comparable to surgical resection.

SABR is gaining interest as a noninvasive treatment option for patients with borderline resectable lung cancers, although further randomized studies are needed to evaluate its survival benefits in operable patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy (SABR) for non-small cell lung cancer. Iyengar, P., Westover, K., Timmerman, RD.[2013]

Stereotactic body radiotherapy (SBRT) is effective for treating early-stage non-small cell lung cancer (NSCLC) in patients who cannot undergo surgery, showing good outcomes and low toxicity for tumors located in the periphery.

However, the risk of severe toxicity increases for tumors near critical structures like the bronchial tree or mediastinum, highlighting the importance of careful dose-fractionation planning in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An optimal dose-fractionation for stereotactic body radiotherapy in peripherally, centrally and ultracentrally located early-stage non-small lung cancer. Zarębska, I., Harat, M.[2023]

In a phase 2 trial involving 40 patients with early-stage non-small cell lung cancer (NSCLC), neoadjuvant stereotactic ablative radiotherapy (SABR) resulted in a pathologic complete response (pCR) rate of 60%, indicating a significant tumor response but lower than expected.

The combined approach of neoadjuvant SABR followed by surgery showed no perioperative mortality and manageable toxicity, with a 2-year overall survival rate of 77%, suggesting it is a safe option for patients fit for surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measuring the Integration of Stereotactic Ablative Radiotherapy Plus Surgery for Early-Stage Non-Small Cell Lung Cancer: A Phase 2 Clinical Trial. Palma, DA., Nguyen, TK., Louie, AV., et al.[2022]

The iSABR trial demonstrated that individualized stereotactic ablative radiotherapy (SABR) for lung tumors resulted in high local control rates, with freedom from local recurrence at 1 year ranging from 94% to 97% across different patient groups.

The trial showed a low incidence of severe toxic effects (only 5%), indicating that personalized dosing strategies can minimize risks while maintaining effective treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Individualized Stereotactic Ablative Radiotherapy for Lung Tumors: The iSABR Phase 2 Nonrandomized Controlled Trial. Gensheimer, MF., Gee, H., Shirato, H., et al.[2023]

In a study of 102 patients treated with stereotactic ablative radiation therapy (SABR) for early-stage non-small-cell lung cancer, a significant correlation was found between higher Biological Equivalent Doses (BED) over 300 Gy and the development of radiological changes such as organizing pneumonia and lung affectation over a 2-year follow-up.

Radiological changes were more pronounced in patients receiving BEDs greater than 300 Gy to healthy lung volumes of at least 30 cc, suggesting that these findings could inform future radiotherapy dose constraints to minimize pulmonary toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological equivalent dose is associated with radiological toxicity after lung stereotactic ablative radiation therapy. Cases, C., Benegas, M., Sánchez, M., et al.[2023]

The TROG 13.01/ALTG 13.001 clinical trial is investigating the safety and efficacy of single versus multi-fraction stereotactic ablative body radiotherapy (SABR) for lung tumors in 84 patients with up to three metastases, aiming to determine the best treatment approach for pulmonary oligometastases.

The study will compare a single high dose of 28Gy to a total of 48Gy delivered in four fractions, assessing not only safety but also quality of life, survival rates, and potential cost implications of each treatment method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised phase II trial of Stereotactic Ablative Fractionated radiotherapy versus Radiosurgery for Oligometastatic Neoplasia to the lung (TROG 13.01 SAFRON II). Siva, S., Kron, T., Bressel, M., et al.[2022]

Stereotactic ablative radiotherapy (SABR) has rapidly expanded in clinical use for treating various primary and metastatic tumors, demonstrating promising results in tumor control.

Despite its effectiveness, SABR can lead to serious complications, highlighting the need for strategies to reduce these risks and improve the safety of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious complications associated with stereotactic ablative radiotherapy and strategies to mitigate the risk. Lo, SS., Sahgal, A., Chang, EL., et al.[2018]

In a study of 39 patients with 45 lung lesions treated with stereotactic ablative body radiotherapy (SBRT), local progression-free survival rates were high, with 90.5% at 1 year and 80.5% at 2 years, indicating effective tumor control.

The treatment was well-tolerated with only mild acute side effects, suggesting that the moderate dose schedules of 35 Gy (5 fractions) or 37.5 Gy (3 fractions) are safe and effective for managing non-small cell lung cancer and metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy for small lung tumors with a moderate dose. Favorable results and low toxicity. Duncker-Rohr, V., Nestle, U., Momm, F., et al.[2022]

Stereotactic ablative radiotherapy (SABR) shows high local control rates of 97.3% at 1 year and 95.7% at 2 years for treating inoperable early-stage small cell lung cancer, based on a meta-analysis of 399 patients across seven studies.

The treatment demonstrates limited toxicity, with only 12.6% of patients experiencing grade 1 toxicity and no severe grade 4 or 5 events reported, indicating that SABR is a safe option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy in T1-2N0M0 small cell lung cancer: A systematic review and meta-analysis. Safavi, AH., Mak, DY., Boldt, RG., et al.[2022]

Stereotactic body radiation therapy (SBRT) is an effective treatment for stage I non-small cell lung cancer, achieving local control in about 90% of patients who cannot undergo surgery.

SBRT involves 3 to 5 treatments over 10 to 14 days and has a relatively low risk of toxicity, making it a preferred option for patients who refuse surgery or are medically inoperable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy for treatment of primary and metastatic pulmonary malignancies. Kelsey, CR., Salama, JK.[2022]

References

1. India pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy for early-stage primary lung cancer, is an active breath coordinator necessary? An audit from a tertiary cancer care center. [2018]

2. Ireland pubmed.ncbi.nlm.nih.gov

Comparison of accelerated hypofractionation and stereotactic body radiotherapy for Stage 1 and node negative Stage 2 non-small cell lung cancer (NSCLC). [2022]

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

Stereotactic ablative radiotherapy (SABR) for non-small cell lung cancer. [2013]

4. Singapore pubmed.ncbi.nlm.nih.gov

An optimal dose-fractionation for stereotactic body radiotherapy in peripherally, centrally and ultracentrally located early-stage non-small lung cancer. [2023]

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

Measuring the Integration of Stereotactic Ablative Radiotherapy Plus Surgery for Early-Stage Non-Small Cell Lung Cancer: A Phase 2 Clinical Trial. [2022]

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

Individualized Stereotactic Ablative Radiotherapy for Lung Tumors: The iSABR Phase 2 Nonrandomized Controlled Trial. [2023]

7. Ireland pubmed.ncbi.nlm.nih.gov

Biological equivalent dose is associated with radiological toxicity after lung stereotactic ablative radiation therapy. [2023]

8. England pubmed.ncbi.nlm.nih.gov

A randomised phase II trial of Stereotactic Ablative Fractionated radiotherapy versus Radiosurgery for Oligometastatic Neoplasia to the lung (TROG 13.01 SAFRON II). [2022]

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

Serious complications associated with stereotactic ablative radiotherapy and strategies to mitigate the risk. [2018]

10. Germany pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy for small lung tumors with a moderate dose. Favorable results and low toxicity. [2022]

11. Ireland pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy in T1-2N0M0 small cell lung cancer: A systematic review and meta-analysis. [2022]

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

Stereotactic body radiation therapy for treatment of primary and metastatic pulmonary malignancies. [2022]