Managing Cancer and Living Meaningfully in Neuro-Oncology: Primary Outcomes from a Randomized Telehealth ORBIT Model Phase IIc Pilot Trial

Abstract Background Individuals with malignant brain tumors experience high rates of psychological distress, including depression and death anxiety, yet are often excluded from supportive care trials. Managing Cancer and Living Meaningfully (CALM) is a brief psychotherapy effective in advanced cancer, but untested in neuro-oncology. This randomized Phase IIc trial is the first controlled evaluation of telehealth CALM in neuro-oncology, assessing feasibility, acceptability, and clinically meaningful effects versus treatment as usual (TAU). Methods Adults with primary (grade III–IV) or secondary brain tumors and elevated depressive and/or death anxiety symptoms were randomized 2:1 to six biweekly CALM sessions or TAU. Mixed methods assessed feasibility of recruitment and data collection, acceptability, and clinically meaningful symptom change. Results Of 105 patients screened, 66% were eligible, 87% consented (N = 60), and 58 were randomized (CALM n = 39; TAU n = 19), supporting feasibility. Among CALM participants, 77% completed treatment, 90% reported high benefit, and all would recommend it. Depressive symptoms decreased in both groups (CALM d = −0.51; TAU d = −0.53). Greater effects were observed for death anxiety (CALM d = −0.95; TAU d = −1.03), with more CALM participants achieving meaningful (63%) and sustained reductions (52%) versus TAU (46% and 25%). Participants reported positive experiences with CALM and telehealth, supporting scalability in neuro-oncology care. Minor improvements were recommended in the study procedures. Conclusions Telehealth CALM is feasible, acceptable, and shows signal for meaningful benefit, particularly for reducing death anxiety, a core yet under-targeted distress domain in malignant brain cancer. Findings address a major gap and support progression to a fully powered Phase III efficacy trial.