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

NSCLC Clinical Trial

Official title:

LEADER Neoadjuvant Screening Trial: LCMC4 Evaluation of Actionable Drivers in Early Stage Lung Cancers

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04712877
• Other study ID #: LCMC LEADER
• Status: Recruiting
• Start date: June 15, 2022
• Est. completion date: June 15, 2025

Study information

• Verified date: September 2023
• Source: Lung Cancer Mutation Consortium
• Contact: Christian Brodala, BBA
• Phone: 646-608-2838
• Email: brodalac[@]mskcc.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: June 15, 2025
• Est. primary completion date: June 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• NSCLC

Intervention

Diagnostic Test:
• ctDNA, tumor NGS
Testing for actionable oncogenic drivers

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Missouri	Columbia	Missouri
United States	University of California, Davis	Davis	California
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	Baylor College of Medicine	Houston	Texas
United States	Dartmouth-Hitchcock	Lebanon	New Hampshire
United States	UCLA	Los Angeles	California
United States	USC Norris Comprehensive Cancer Center	Los Angeles	California
United States	St. Joseph's Hospital Orange	Orange	California
United States	Washington University	Saint Louis	Missouri
United States	University of Washington	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Lung Cancer Mutation Consortium	Lung Cancer Research Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Tumor Mutation Burden (TMB) Assessment	Measure TMB in all patient tumor samples (Mutations per megabase)	8 weeks