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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if local ablative therapy (LAT), which targets and destroys specific cancer sites, can better control non-small cell lung cancer (NSCLC) than usual systemic treatments when minimal residual disease (tiny traces of cancer) is rising. The study will compare LAT's effectiveness against standard therapies in patients with metastatic NSCLC. It suits patients with stage IV NSCLC who have ten or fewer metastatic lesions and have already begun standard first-line treatments. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to explore new treatment options.

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 prior data suggests that local ablative therapy is safe for treating non-small cell lung cancer?

Research has shown that local ablative therapy (LAT), often performed using stereotactic ablative radiotherapy (SABR), is generally safe for treating non-small cell lung cancer (NSCLC). Studies have found that SABR is well-tolerated by patients, with few serious side effects. For instance, a review of several studies reported low rates of harmful effects from SABR.

Another study found that SABR is not only effective but also safe for patients who cannot undergo surgery. Over five years, this study showed that patients experienced good safety outcomes, meaning the treatment did not cause major health problems over time.

While no treatment is without risks, current research provides encouraging safety information for those considering local ablative therapy for NSCLC. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about local ablative therapy for non-small cell lung cancer (NSCLC) because it offers a targeted approach by directly destroying cancer cells at specific sites, unlike traditional systemic therapies like chemotherapy and immunotherapy that affect the whole body. This method can potentially reduce tumor burden more precisely and quickly without the widespread side effects often seen with standard treatments. Additionally, local ablative therapy could provide a new avenue for patients whose cancer hasn't progressed visibly on scans but still shows molecular activity, offering hope for extending progression-free survival.

What evidence suggests that local ablative therapy could be effective for non-small cell lung cancer?

Research has shown that local treatments like stereotactic ablative radiotherapy (SABR), studied in this trial as local ablative therapy, hold promise for treating non-small cell lung cancer (NSCLC). Studies have found that SABR can control cancer by preventing growth at its original site. Additionally, SABR is associated with longer survival rates, as patients tend to live longer when the cancer is controlled. Importantly, this treatment causes fewer side effects compared to other options. These findings suggest that local treatments could effectively manage metastatic NSCLC, especially when addressing increasing levels of minimal residual disease (MRD). In this trial, some participants will receive local ablative therapy to all sites of disease, while others will continue with standard systemic therapy. ^{1 3 5 6 7}

Who Is on the Research Team?

Daniel Gomez

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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]

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 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) 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 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5601509/

A systematic review of outcomes following stereotactic ... Even with the increasing number of patient outcome data being published on SABR in early-stage (ES) non-small-cell lung cancer (NSCLC), phase III evidence ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0167814024007096

Stereotactic ablative radiotherapy for locally advanced non ... This meta-analysis presents promising findings regarding LC and OS rates, while also observing low toxicity rates, indicating the potential feasibility of SABR ...

3. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2823972

Stereotactic vs Hypofractionated Radiotherapy for ... This randomized clinical trial examines whether stereotactic body radiotherapy improves local control compared with hypofractionated conventional.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05291780

NCT05291780 | Stereotactic Ablative Radiotherapy in ... The purpose of this study is to explore SABR in the treatment of unresectable LA-NSCLC. Official Title. STereotactic Ablative RadioTherapy in NEWly Diagnosed ...

5. thegreenjournal.com thegreenjournal.com/article/S0167-8140(14)00541-6/fulltext

Management of early-stage non-small cell lung cancer ... Study of 201 non-small cell lung cancer patients given stereotactic ablative radiation therapy shows local control dependence on dose calculation algorithm.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12268857/

Stereotactic ablative body radiation therapy for treatment of ... Stereotactic ablative radiotherapy (SABR) has emerged as the standard treatment for medically inoperable early-stage non-small cell lung cancer ...

7. redjournal.org redjournal.org/article/S0360-3016(25)06209-1/abstract

5-year survival and safety of stereotactic ablative ... The 5-year outcomes of XXXX trial confirm robust and sustained benefit in terms of safety and effectiveness of SAbR in LA-NSCLC patients unfit ...