title: A Brief Report of the Status of Central Nervous System Metastasis Enrollment Criteria for Advanced Non-Small Cell Lung Cancer Clinical Trials: A Review of the ClinicalTrials.gov Trial Registry.
abstract: BACKGROUND
  Central nervous system (CNS) metastases are common in non-small cell lung cancer (NSCLC), yet clinical trials of new drugs in advanced NSCLC have varying inclusion and exclusion criteria for CNS disease. The true extent of variation in CNS-related enrollment criteria in NSCLC clinical trials has not been documented.
  
  
  METHODS
  We performed a systematic search of the ClinicalTrials.gov website to characterize interventional drug trials enrolling adult patients with advanced NSCLC.
  
  
  RESULTS
  Of 413 open trials, 78 (19%) strictly excluded patients with leptomeningeal disease (LMD). Separate from LMD, patients with any history of CNS metastases were strictly excluded in 59 trials (14%), allowed after local treatment in 169 (41%), and allowed with no prior treatment in 106 (26%). No explicit mention of CNS disease was made in 79 trials (19%). In multivariate analysis looking at trial phase, location, sponsor, and treatment type, only sponsor was statistically significant, with pharmaceutical industry-sponsored trials having higher odds of excluding patients with brain metastases than did university or investigator-initiated trials (OR = 2.262, 95% confidence interval: 1.063-4.808, p = 0.0342) CONCLUSIONS: With 14% to 19% of trials excluding any history of LMD or CNS parenchymal metastatic disease and 41% of trials permitting CNS disease only after prior CNS-directed treatment, direct evidence of activity of a treatment on CNS disease cannot be reliably generated in most NSCLC trials. Given the high frequency of CNS disease in NSCLC and only sponsor being associated with specific CNS exclusion criteria, sponsors should consider tailoring trial designs to explore CNS benefit more explicitly.
authors.affiliation: Division of Medical Oncology, University of Colorado, Denver, CO, USA. Electronic address: Caroline.McCoach@ucdenver.edu.
authors.forename: Caroline E
authors.initials: CE
authors.lastname: McCoach
authors.affiliation: Division of Medical Oncology, University of Colorado, Denver, CO, USA.
authors.forename: Eamon M
authors.initials: EM
authors.lastname: Berge
authors.affiliation: Department of Biostatistics and Informatics, Colorado School of Public Health, Denver, CO, USA.
authors.forename: Xian
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Biostatistics and Informatics, Colorado School of Public Health, Denver, CO, USA.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Barón
authors.affiliation: Division of Medical Oncology, University of Colorado, Denver, CO, USA.
authors.forename: D Ross
authors.initials: DR
authors.lastname: Camidge
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012042:Registries; D055815:Young Adult
keywords: CNS metastases; Clinical trial enrollment; Clinicaltrials.gov; Leptomeningeal disease; NSCLC