Clrm-11 current state of clinical trials for patients with melanoma brain metastases

Abstract INTRODUCTION Clinical trials have traditionally excluded patients with melanoma brain metastasis (MBM), despite evidence of CNS activity of systemic therapy. The true extent of variation in MBM-related enrollment criteria in ongoing melanoma clinical trials has not been evaluated. METHODS A systematic search of clinicaltrials.gov website was performed to characterize trends in clinical trial enrollment of MBM patients in interventional drug trials. Trial data search was limited to “open”, “interventional studies” and advanced stage melanoma in adult patients. Logistic regression was used to model inclusion of active MBMs. Covariates considered were phase of study, location, therapy type, melanoma specific, and sponsor category RESULTS Of a total of 475 trials identified, 365 met inclusion criteria. 230 (63.0%) were phase I, 119 (32.6%) were phase II, 14 (3.8%) were phase III and 2 (0.5%) were phase IV trials. 184 (50.4%) were pharmaceutical industry sponsored, 183 (50.1%) were specific for melanoma. Forty-seven (12.8%) trials strictly excluded brain metastasis and 173 (47.3%) strictly excluded leptomeningeal disease (LMD). 261 (71.5%) trials allowed patients with previously treated MBM, and 73 (20.0%) allowed patients with active MBMs. No explicit mention of CNS metastasis was made in 13.6% of trials and no mention of LMD was made in 43.8% trials. In univariate models, trials not employing immunotherapy (odds ratio 2.23; 95% CI: 1.2, 4.3; p = 0.0174) and non-pharma trials (odds ratio 1.98; 95% CI 1.0, 3.9; p= 0.0461) were twice as likely to include MBM patients. In a combined model, only therapy type remained significant at the α=0.05 level. CONCLUSION Despite the evidence of CNS activity of immunotherapy in randomized trials, only 20% ongoing trials are enrolling patients with active MBMs. Efforts should be made to tailor future clinical trial designs to include MBM patients to assess CNS activity of systemic therapeutics early on in drug development.