RMTC-09 EXCLUSION OF PATIENTS WITH BRAIN METASTASES FROM EARLY-PHASE SYSTEMIC THERAPY TRIALS: A CROSS-SECTIONAL ANALYSIS OF ELIGIBILITY CRITERIA
Cody Zatzman, Italo Fernandes, Natasha D’Souza, Evan Cescon, Eva Zhang, Meghna Katyal, Farideh Tavangar, Ines Menjak, Martin Smoragiewicz, Katarzyna JerzakAbstract
Introduction
Patients with brain metastases (BrM) are frequently excluded from early-phase clinical trials, limiting evaluation of central nervous system (CNS) efficacy of novel therapies. We aimed to determine the proportion of phase I systemic therapy trials for metastatic solid tumors that exclude patients with BrM.
Methods
In July 2024, ClinicalTrials.gov was systematically searched using the term “cancer.” Phase I systemic therapy trials enrolling patients with metastatic solid tumors were included. Only trials with publicly available protocols were analyzed. Trial characteristics were independently abstracted by four reviewers, and eligibility criteria were assessed for BrM exclusion.
Results
Of 3,210 identified studies, 1,752 met inclusion criteria, and 871 trials with available protocols were analyzed. Breast cancer, lung cancer, and melanoma trials comprised 7.6% (n = 66/871), 12.6% (n = 110/871), and 4.4% (n = 38/871), respectively; mixed tumor types accounted for 58.4% (n = 509/871). Investigational therapies included cytotoxic chemotherapy (5.1%, n = 44/871), targeted therapy (15.0%, n = 131/871), immunotherapy (43.7%, n = 381/871), and combination approaches. Patients with BrM were eligible with restrictions in 70.4% (n = 613/871) of trials and excluded in 13.2% (n = 115/871); BrM were not specified in the inclusion/exclusion criteria of 16.4% (n = 143/871) of trial protocols. Among trials permitting restricted enrollment (n = 613) of patients with BrM, patients with symptomatic BrM (58.6%, n = 361/613), untreated BrM (76.0%, n = 468/613), and active/unstable BrM (83.9%, n = 517/613) were frequently excluded. Trials initiated from 2015 onward were more likely to permit inclusion of patients with BrM than those initiated between 2000–2014 (72.2%, n = 458/634 vs. 65.4%, n = 155/237). Trials evaluating cytotoxic chemotherapy more commonly excluded patients with BrM (31.8%, n = 14/44) compared to those investigating targeted therapies (10.7%, n = 14/131) and immunotherapy (10.5%, n = 40/381).
Conclusion
Inclusion of patients with BrM in phase I trials has improved over time, particularly in studies evaluating targeted therapies and immunotherapy. However, restrictive eligibility criteria, particularly exclusion of patients with symptomatic, untreated, or “active” BrM, remain common.