Clinical trial NCT04712877: 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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: NSCLC
Lead sponsor: Lung Cancer Mutation Consortium
Sponsor class: NETWORK
Collaborators: name: Lung Cancer Research Foundation
First posted: 2021-01-15
Enrollment: 1000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.


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

Primary outcomes:
measure: Proportion of Patients who Possess Actionable Oncogenic Drivers
timeFrame: 8 weeks
Secondary outcomes:
measure: Tumor Mutation Burden (TMB) Assessment
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Davis
country: United States
facility: University of California, Davis
state: California
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Orange
country: United States
facility: St. Joseph's Hospital Orange
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Columbia
country: United States
facility: University of Missouri
state: Missouri
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock
state: New Hampshire
city: New York
country: United States
facility: NYU
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: Brigham and Women's Hospital
name: Scott J Swanson, MD
role: PRINCIPAL_INVESTIGATOR
References: