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

NCT04712877 | Recruiting

• 1 other identifier: LCMC LEADER
• Study Type: observational
• Target: 1,000
• Locations: 1 country
• Sites: 21

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.

Conditions

NSCLC

Outcome Measures

Primary Outcomes (1)

• Proportion of Patients who Possess Actionable Oncogenic Drivers

  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.

  8 weeks

Secondary Outcomes (1)

• Tumor Mutation Burden (TMB) Assessment

  8 weeks

Interventions

ctDNA, tumor NGS DIAGNOSTIC_TEST

Testing for actionable oncogenic drivers

Also known as: FoundationOne CDx, FoundationOne Liquid

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The LCMC 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.

You may qualify if:

• Clinical stage IA2-III lung cancers
• Potentially resectable if lung cancer suspicion confirmed pathologically
• Operable

You may not qualify if:

• No concurrent malignancy
• No prior lung cancer within last 2 years
• Purely ground glass pulmonary opacity

Sponsors & Collaborators

• Lung Cancer Mutation Consortium: lead
• Lung Cancer Research Foundation: collaborator

Study Sites (21)

University of California, Davis

Davis, California, 95616, United States

RECRUITING

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

RECRUITING

UCLA

Los Angeles, California, 90095, United States

RECRUITING

St. Joseph's Hospital Orange

Orange, California, 92868, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Boston Medical Center

Boston, Massachusetts, 02118, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

University of Missouri

Columbia, Missouri, 65212, United States

RECRUITING

Washington University

St Louis, Missouri, 63110, United States

RECRUITING

Dartmouth-Hitchcock

Lebanon, New Hampshire, 03756, United States

RECRUITING

NYU

New York, New York, 10016, United States

RECRUITING

Columbia University

New York, New York, 10032, United States

RECRUITING

Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

RECRUITING

Baylor College of Medicine

Houston, Texas, 77030, United States

RECRUITING

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

RECRUITING

University of Washington

Seattle, Washington, 98019, United States

RECRUITING

Study Officials

• Scott J Swanson, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christian Brodala, BBA

CONTACT

646-608-2838; brodalac@mskcc.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NETWORK
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Canepari Family Distinguished Chair in Thoracic Surgery, Director of Minimally Invasive Thoracic Surgery and Clinical Director of Thoracic Surgery, BWH, Associate Chief of Surgery, DFCI, Professor of Surgery, Harvard Medical School

Study Record Dates

• First Submitted: October 16, 2020
• First Posted: January 15, 2021
• Study Start: June 15, 2022
• Primary Completion: June 15, 2025
• Study Completion (Estimated): June 15, 2026
• Last Updated: July 17, 2024

Record last verified: 2024-07

Locations

US (21)