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A Study of Local Ablative Therapy (LAT) in People With Non-Small Cell Lung Cancer (NSCLC)

Phase 2
Recruiting
Conditions
Minimal Residual Disease
Non Small Cell Lung Cancer Metastatic
Non-small Cell Lung Cancer
Nsclc
Metastatic Non Small Cell Lung Cancer
NSCLC Stage IV
Interventions
Procedure: Local ablative therapy
Other: Blood collection to assess for ctDNA
Registration Number
NCT05429320
Lead Sponsor
Memorial Sloan Kettering Cancer Center
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
90
Inclusion Criteria

Not provided

Exclusion Criteria
  • At the time of therapeutic phase enrollment, complete response radiographically (no lesions to target)
  • Patients with CNS-only disease (due to limited capacity of peripheral blood ctDNA to detect CNS lesions)
  • Planned treatment by targeted agents (e.g. tyrosine kinase inhibitors) or patient not a candidate for systemic therapy
  • Serious medical co-morbidities precluding radiotherapy or ablation, determined at the discretion of the treating investigator.
  • At the time of therapeutic phase enrollment, pregnant or lactating women.
  • Physical limitation to undergo stereotactic radiotherapy.
  • Other active malignancy within the last year except for basal cell carcinoma of the skin and in situ malignancy even if without evidence of disease.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Part ILocal ablative therapyIn 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.
Part IBlood collection to assess for ctDNAIn 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.
Part II - standard of careBlood collection to assess for ctDNAIf 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.
Part II - ablation to all sites of disease (experimental arm)Local ablative therapyIf 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.
Part II - ablation to all sites of disease (experimental arm)Blood collection to assess for ctDNAIf 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.
Primary Outcome Measures
NameTimeMethod
Progression Free Survival/PFS3 months +/- 2 weeks after enrollment

PFS will be evaluated through imaging obtained Q3 months +/-2 weeks after enrollment. Progression will be evaluated by RECIST 1.1 guidelines. To determine whether LAT improves PFS in patients with metastatic NSCLC who have NR-VAF but no radiographic progression of disease compared to patients who continue systemic therapy.

Measure the reduction in mean variant allele frequency/VAF by 6 months after Local Ablative Therapy/LAT6 months

To determine whether Local Ablative Therapy/LAT (ablation to all sites of disease) causes a reduction in mean variant allele frequency/VAF by 6 months after LAT in patients with metastatic NSCLC who have non-responding variant allele frequency/NR-VAF (\<50% reduction in mean VAF) but no radiographic progression of disease. Mean VAF: Mean VAF will be defined by the VAF of each relevant mutation divided by the total number of mutations

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (9)

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

🇺🇸

New York, New York, United States

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

🇺🇸

Harrison, New York, United States

Hartford Healthcare ALLIANCE (Data collection only)

🇺🇸

Hartford, Connecticut, United States

Memorial Sloan Kettering Suffolk-Commack (Limited Protocol Activities)

🇺🇸

Commack, New York, United States

BAPTIST ALLIANCE - MCI (Data collection only)

🇺🇸

Miami, Florida, United States

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

🇺🇸

Uniondale, New York, United States

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

🇺🇸

Montvale, New Jersey, United States

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

🇺🇸

Middletown, New Jersey, United States

Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities)

🇺🇸

Basking Ridge, New Jersey, United States

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