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

• ClinicalTrials.gov Identifier: NCT04712877
• Recruitment Status: Recruiting
• First Posted: January 15, 2021
• Last Update Posted: September 13, 2023
• Sponsor: Lung Cancer Mutation Consortium
• Collaborator: Lung Cancer Research Foundation
• Information provided by (Responsible Party): Scott J. Swanson, Brigham and Women's Hospital

Tracking Information

• First Submitted Date: October 16, 2020
• First Posted Date: January 15, 2021
• Last Update Posted Date: September 13, 2023
• Actual Study Start Date: June 15, 2022
• Estimated Primary Completion Date: June 15, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 14, 2021)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 14, 2021)

Tumor Mutation Burden (TMB) Assessment [ Time Frame: 8 weeks ]

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Testing Tumor Tissue and Blood to Help Select Personalized Treatments for Patients With Suspected Lung Cancers
• Official Title: LEADER Neoadjuvant Screening Trial: LCMC4 Evaluation of Actionable Drivers in Early Stage Lung Cancers

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.

• Detailed Description: Not Provided
• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• 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.
• Condition: NSCLC

Intervention

Diagnostic Test: ctDNA, tumor NGS

Testing for actionable oncogenic drivers

Other Names:

• FoundationOne CDx
• FoundationOne Liquid

• Study Groups/Cohorts: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 14, 2021): 1000
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 15, 2025
• Estimated Primary Completion Date: June 15, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04712877
• Other Study ID Numbers: LCMC LEADER
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Scott J. Swanson, Brigham and Women's Hospital
• Original Responsible Party: Boris Sepesi, M.D. Anderson Cancer Center, Associate Professor, Department of Thoracic and Cardiovascular Surgery,
• Current Study Sponsor: Lung Cancer Mutation Consortium
• Original Study Sponsor: Lung Cancer Research Foundation
• Collaborators: Lung Cancer Research Foundation

Investigators

• Principal Investigator: Scott J Swanson, MD; Brigham and Women's Hospital

• PRS Account: Lung Cancer Mutation Consortium
• Verification Date: September 2023