MB-PAT for Demoralization in Advanced Cancer ('PAT-MIND') Trial

PAT‐MIND is a multi‐site, phase IIb pilot feasibility and therapy‐optimization trial ofpsilocybin‐assisted therapy in adults with advanced cancer. The study uses awave‐randomized 2×2 factorial design to examine two intervention components: psilocybindose and psychotherapy intensity. Participants will be enrolled in small waves, and eachwave will be randomized to one of four combinations: high‐dose psilocybin plusmindfulness‐based psilocybin‐assisted therapy, high‐dose psilocybin plus standardpsilocybin‐assisted therapy, low‐dose psilocybin plus mindfulness‐basedpsilocybin‐assisted therapy, or low‐dose psilocybin plus standard psilocybin‐assistedtherapy.The psilocybin dose comparison is blinded. Participants will receive either 25 mg or 5 mgpsilocybin during a monitored in‐person group dosing session. The psychotherapy intensitycomparison is not blinded. Participants will receive either mindfulness‐basedpsilocybin‐assisted therapy or standard psilocybin‐assisted therapy, depending on theirrandomized intervention combination. Preparation and integration sessions will bedelivered using a hybrid format, with some sessions conducted in person and somevirtually, depending on the session type and site logistics.The primary aims of this pilot trial are to assess the feasibility, acceptability, andsafety of hybrid group‐based psilocybin‐assisted therapy in adults with advanced cancer,and to explore therapy‐optimization signals for psilocybin dose and psychotherapyintensity to inform a future definitive trial. Exploratory objectives include participantexperience, demoralization, secondary psychological outcomes, health‐related quality oflife, health‐economic measures, and exploratory biomarker outcomes.Study procedures include screening, informed consent, trial‐specific questionnaires,group and individual preparation and integration sessions, a monitored psilocybin dosingday, dried blood spot collection, stool sample collection, optional wearable device datacollection, and medical chart review. Participants will complete online questionnaires atprotocol‐defined timepoints, including measures of demoralization, psychologicaldistress, quality of life, treatment experience, and resource use.Safety will be monitored throughout the study, including adverse event monitoring duringand after the dosing session.