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Testing Tumor Tissue and Blood to Help Select Personalized Treatments for Patients With Suspected Lung Cancers

Recruiting
Conditions
NSCLC
Registration Number
NCT04712877
Lead Sponsor
Lung Cancer Mutation Consortium
Brief Summary

This collaborative screening protocol, developed by the Lung Cancer Mutation Consortium (LCMC) and supported by the Thoracic Surgery Oncology Group (TSOG), is designed to determine the feasibility of comprehensive molecular profiling to detect actionable oncogenic drivers in patients with suspected early stage lung cancers scheduled to undergo biopsies to establish the diagnosis of lung cancer.

The primary purpose of this testing is to determine the presence of 12 oncogenic drivers (mutations in EGFR, BRAFV600E , MET exon 14, KRAS G12C and HER2, rearrangements in ALK, RET, NTRK, EGFR exon 20 insertion and ROS1, and amplification of MET and HER2) that can serve as targets making patients eligible for upcoming targeted neoadjuvant therapy trials. The ultimate goal is to use this information from the screening process to select the optimal neoadjuvant therapy and wherever possible enroll patients onto separate neoadjuvant therapy trials with genomically matched treatments or other appropriate trials if no actionable driver mutation is detected.

Thoracic Surgery Oncology Group (TSOG) is a network of surgeons within North American Thoracic Surgery Academic Centers aligned with the goal of enhancing patient care through administration of multi-site trials focused on recent advances in lung cancer. TSOG has aligned with the LCMC4 sites to enroll the LCRF-LEADER screening trial. TSOG's involvement will be essential in trial enrollment and ultimate interpretation of the multimodal clinical and translational data collected as part of this study. We estimate we will detect an actionable oncogenic driver in 33% of cases. The remaining 66% of patients will represent a cohort identified by their care teams as candidates for other potential neoadjuvant therapies which may include checkpoint inhibitors such as atezolizumab, durvalumab, nivolumab, and pembrolizumab or other novel agents.

The targeted therapy treatment trials will be conducted independently of the LCRF-LEADER screening trial, evaluating for efficacy. If none of the 10 oncogenic drivers are detected, the patient will be offered participation in any clinical trial of neoadjuvant therapy available at their treating institution or standard of care therapy. For patients not enrolled on a targeted treatment trial, circulating tumor DNA in blood (ctDNA) will be collected at 3 time points: before neoadjuvant treatment, after neoadjuvant treatment but before surgery, and after surgery. This initiative will be correlated with various clinical outcomes. Prespecified clinical data will be collected for correlation with these circulating biomarkers.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
1000
Inclusion Criteria
  • Clinical stage IA2-III lung cancers
  • Potentially resectable if lung cancer suspicion confirmed pathologically
  • Operable
Exclusion Criteria
  • No concurrent malignancy
  • No prior lung cancer within last 2 years
  • Purely ground glass pulmonary opacity

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Proportion of Patients who Possess Actionable Oncogenic Drivers8 weeks

The primary outcome measure is the determination of the proportion of patients with stage IA2-III lung cancers who possess actionable oncogenic drivers. A patient is considered to have a actionable oncogenic driver if they have any of the following 10 genomic alterations: ALK rearrangements, BRAFV600E mutations, EGFR sensitizing mutations, HER2 mutation, HER2 amplification, MET amplification, MET exon 14 mutation, RET rearrangements, NTRK rearrangement, or ROS1 rearrangements.

Secondary Outcome Measures
NameTimeMethod
Tumor Mutation Burden (TMB) Assessment8 weeks

Measure TMB in all patient tumor samples (Mutations per megabase)

Trial Locations

Locations (21)

University of Missouri

🇺🇸

Columbia, Missouri, United States

Boston Medical Center

🇺🇸

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

USC Norris Comprehensive Cancer Center

🇺🇸

Los Angeles, California, United States

UCLA

🇺🇸

Los Angeles, California, United States

St. Joseph's Hospital Orange

🇺🇸

Orange, California, United States

Northwestern University

🇺🇸

Chicago, Illinois, United States

Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

Brigham and Women's Hospital

🇺🇸

Boston, Massachusetts, United States

Dartmouth-Hitchcock

🇺🇸

Lebanon, New Hampshire, United States

Washington University

🇺🇸

Saint Louis, Missouri, United States

NYU

🇺🇸

New York, New York, United States

Columbia University

🇺🇸

New York, New York, United States

Ohio State University

🇺🇸

Columbus, Ohio, United States

Virginia Cancer Specialists, PC

🇺🇸

Fairfax, Virginia, United States

University of Washington

🇺🇸

Seattle, Washington, United States

Baylor College of Medicine

🇺🇸

Houston, Texas, United States

University of California, Davis

🇺🇸

Davis, California, United States

Moffitt Cancer Center

🇺🇸

Tampa, Florida, United States

University of Michigan

🇺🇸

Ann Arbor, Michigan, United States

Medical University of South Carolina

🇺🇸

Charleston, South Carolina, United States

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