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

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ClinicalTrials.gov Identifier: NCT04712877
Recruitment Status : Recruiting
First Posted : January 15, 2021
Last Update Posted : November 14, 2022
Lung Cancer Research Foundation
Information provided by (Responsible Party):
Boris Sepesi, M.D. Anderson Cancer Center

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 10 oncogenic drivers (mutations in EGFR, BRAFV600E , MET exon 14, and HER2, rearrangements in ALK, RET, NTRK, 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.

Condition or disease Intervention/treatment
NSCLC Diagnostic Test: ctDNA, tumor NGS

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Study Type : Observational
Estimated Enrollment : 1000 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: LEADER Neoadjuvant Screening Trial: LCMC4 Evaluation of Actionable Drivers in Early Stage Lung Cancers
Actual Study Start Date : June 15, 2022
Estimated Primary Completion Date : June 15, 2024
Estimated Study Completion Date : June 15, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Intervention Details:
  • Diagnostic Test: ctDNA, tumor NGS
    Testing for actionable oncogenic drivers
    Other Names:
    • FoundationOne CDx
    • FoundationOne Liquid

Primary Outcome Measures :
  1. Proportion of Patients who Possess Actionable Oncogenic Drivers [ Time Frame: 8 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 :
  1. Tumor Mutation Burden (TMB) Assessment [ Time Frame: 8 weeks ]
    Measure TMB in all patient tumor samples (Mutations per megabase)

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
The LCRF LEADER screening trial will enroll all patients with clinically suspected, resectable stage I-III lung cancers. The population of interest is patients with resectable non-squamous non-small cell lung cancer, however a histologic diagnosis is not required at the time of study enrollment. We anticipate a small portion of patients with squamous cell and non-NSCLC histologies to be genotyped centrally in parallel to their histologic diagnosis. Only patients with non-small cell lung cancers that are not purely squamous will be counted towards the primary study endpoint.

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04712877

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Contact: Christian Brodala, BBA 646-608-2838 brodalac@mskcc.org

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United States, California
University of California, Davis Recruiting
Davis, California, United States, 95616
Contact: Ashley Dang-Chu       ldangchu@ucdavis.edu   
Principal Investigator: Tianhong Li, MD, PhD         
USC Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Peggy Romano       peggy.romano@med.usc.edu   
Principal Investigator: Sean Wightman, MD         
St. Joseph's Hospital Orange Recruiting
Orange, California, United States, 92868
Contact: Ron Bati       Ron.Bati@stjoe.org   
Principal Investigator: John Maurice, MD         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Shari Barnett       shbailey@med.umich.edu   
Principal Investigator: Jules Lin, MD         
United States, Washington
University of Washington Recruiting
Seattle, Washington, United States, 98019
Contact: Lara Schiff       lschiff1@seattlecca.org   
Principal Investigator: Christina Baik, MD, MPH         
Sponsors and Collaborators
Lung Cancer Mutation Consortium
Lung Cancer Research Foundation
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Principal Investigator: Boris Sepesi, MD M.D. Anderson Cancer Center
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Responsible Party: Boris Sepesi, Associate Professor, Department of Thoracic and Cardiovascular Surgery,, M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT04712877    
Other Study ID Numbers: LCMC LEADER
First Posted: January 15, 2021    Key Record Dates
Last Update Posted: November 14, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No