Advanced Cancer, Demoralization, Existential Distress, Psychological Distress
Conditions
Keywords
psychedelics, psilocybin, cancer, demoralization, late-stage, psychedelic-assisted therapy, PAT, Mindfulness, existential distress
Brief summary
This pilot clinical trial will study psilocybin-assisted therapy for adults with advanced cancer who are experiencing demoralization, existential distress, or related psychological concerns. Demoralization can include feelings of hopelessness, helplessness, loss of meaning, and distress related to illness or end of life. The purpose of this study is to assess whether a hybrid group-based psilocybin-assisted therapy program is feasible, acceptable, and safe in adults with advanced cancer. The study will also explore which combination of psilocybin dose and psychotherapy approach may be most promising for a future larger trial. Participants will be randomly assigned by wave to one of four intervention combinations: 25 mg psilocybin with mindfulness-based psilocybin-assisted therapy, 25 mg psilocybin with standard psilocybin-assisted therapy, 5 mg psilocybin with mindfulness-based psilocybin-assisted therapy, or 5 mg psilocybin with standard psilocybin-assisted therapy. The psilocybin dose will be blinded, meaning participants and some members of the study team will not know which dose was assigned. Psychotherapy approach will not be blinded. The study will enroll at least 60 participants across Calgary and Kingston.
Detailed description
PAT-MIND is a multi-site, phase IIb pilot feasibility and therapy-optimization trial of psilocybin-assisted therapy in adults with advanced cancer. The study uses a wave-randomized 2×2 factorial design to examine two intervention components: psilocybin dose and psychotherapy intensity. Participants will be enrolled in small waves, and each wave will be randomized to one of four combinations: high-dose psilocybin plus mindfulness-based psilocybin-assisted therapy, high-dose psilocybin plus standard psilocybin-assisted therapy, low-dose psilocybin plus mindfulness-based psilocybin-assisted therapy, or low-dose psilocybin plus standard psilocybin-assisted therapy. The psilocybin dose comparison is blinded. Participants will receive either 25 mg or 5 mg psilocybin during a monitored in-person group dosing session. The psychotherapy intensity comparison is not blinded. Participants will receive either mindfulness-based psilocybin-assisted therapy or standard psilocybin-assisted therapy, depending on their randomized intervention combination. Preparation and integration sessions will be delivered using a hybrid format, with some sessions conducted in person and some virtually, depending on the session type and site logistics. The primary aims of this pilot trial are to assess the feasibility, acceptability, and safety of hybrid group-based psilocybin-assisted therapy in adults with advanced cancer, and to explore therapy-optimization signals for psilocybin dose and psychotherapy intensity to inform a future definitive trial. Exploratory objectives include participant experience, demoralization, secondary psychological outcomes, health-related quality of life, 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 dosing day, dried blood spot collection, stool sample collection, optional wearable device data collection, and medical chart review. Participants will complete online questionnaires at protocol-defined timepoints, including measures of demoralization, psychological distress, quality of life, treatment experience, and resource use. Safety will be monitored throughout the study, including adverse event monitoring during and after the dosing session.
Interventions
DRUGPEX010 25 mg psilocybin
Participants randomized to this dose condition will receive a single 25 mg oral dose of PEX010 (psilocybin) during a monitored in-person group dosing session, together with protocol-defined psychotherapeutic support
DRUGPEX010 5 mg psilocybin
Participants randomized to this dose condition will receive a single 5 mg oral dose of PEX010 (psilocybin) during a monitored in-person group dosing session, together with protocol-defined psychotherapeutic support. This is a blinded low-dose active comparator condition.
BEHAVIORALStandard Psilocybin-Assisted Therapy
Participants randomized to this psychotherapy condition will receive standard psilocybin-assisted therapy, including protocol-defined preparation, dosing-day support, and integration sessions. The intervention is delivered in a hybrid format, with some sessions conducted in person and some virtually, depending on session type and site logistics.
BEHAVIORALMindfulness-Based Psilocybin-Assisted Therapy
Participants randomized to this psychotherapy condition will receive mindfulness-based psilocybin-assisted therapy, including protocol-defined preparation, dosing-day support, and integration sessions. The intervention includes mindfulness-based therapeutic elements and is delivered in a hybrid format, with some sessions conducted in person and some virtually, depending on session type and site logistics.
Sponsors
University of Calgary
Providence Care, Kingston, ON, Canada
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Phase IIb pilot feasibility and therapy-optimization trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent provided before any study-specific procedures. * Age 18 years or older. * Diagnosis of advanced cancer: Stage III-IV or metastatic solid tumor. Stage II cancer may be eligible if the treating oncologist confirms advanced/refractory disease with clinically significant existential burden, defined as a Demoralization Scale-II (DS-II) score ≥11. * Clinical life expectancy of at least 6 months. Borderline cases of approximately 5-6 months may be considered based on Principal Investigator judgment and documentation. * Demoralization Scale-II (DS-II) total score ≥4 at screening, or DS-II total score ≥3 with documented clinical impression of significant existential distress. * Willing and cognitively able to complete at least 2 preparation sessions, 1 in-person dosing session, and at least 2 integration sessions over approximately 6-8 weeks. * Sufficient spoken and written English proficiency to provide informed consent, participate in group therapy, and complete participant-reported outcome measures. * Not pregnant or lactating. Participants of childbearing potential must have a negative pregnancy test at screening and comply with protocol-specified contraception requirements. * A responsible adult, such as a family member, friend, or caregiver, must be available to accompany the participant or be on-call for at least 12 hours following the dosing session.
Exclusion criteria
Psychiatric/Psychological: * Active or high-risk suicidality, defined as Columbia-Suicide Severity Rating Scale (C-SSRS) item 4 or 5 within the past 4 weeks, or a suicide attempt within the past 12 months. Passive death wishes and suicidal ideation without intent are not exclusionary. * Current psychotic disorder or active psychotic symptoms, including schizophrenia, schizoaffective disorder, hallucinations, delusions, or thought disorganization. Historical psychosis in sustained remission may be considered on a case-by-case basis by the Principal Investigator. * Current manic or mixed-state episode. Stable, euthymic bipolar disorder on maintenance pharmacotherapy may be permitted with Principal Investigator judgment and documentation. * Moderate-to-severe active alcohol, stimulant, or opioid use disorder within the past 12 months. Severe uncontrolled cannabis use disorder is exclusionary; stable prescribed cannabis use is permitted. Pharmacological/Drug Interactions: * Use of concomitant medications that does not meet the requirements of the protocol-specified Concomitant Medications Policy. * Known allergy, anaphylaxis, or serious hypersensitivity to psilocybin, psilocin, related tryptamines, or capsule excipients. Medical: * Severe hepatic impairment, defined as a current unstable diagnosis of liver disease with AST or ALT \>5 times the upper limit of normal and clinical symptoms. * Severe renal impairment, including current unstable acute kidney injury or advanced kidney disease (CKD Stage 4) with eGFR \<30 mL/min/1.73 m². * Unstable cardiovascular disease, including myocardial infarction or stroke within the past 3 months, decompensated heart failure (NYHA III-IV), or uncontrolled arrhythmia. Elevated blood pressure on dosing day may require dosing deferral and reassessment according to protocol-defined thresholds. * Seizure within the past 12 months or currently uncontrolled epilepsy. Well-controlled epilepsy with no seizures for more than 12 months on stable therapy may be permitted with monitoring. * Uncontrolled diabetes, including unstable Type 1 diabetes with diabetic ketoacidosis within the past 3 months, or Type 2 diabetes with HbA1c \>11% and symptomatic hyperglycemia. * Any medical, neurological, or psychiatric condition, or concurrent cancer-directed therapy, that in the Principal Investigator's clinical judgment would materially increase risk or prevent meaningful protocol participation. Cancer Treatment-Related: * Systemic anti-cancer therapy that does not meet protocol requirements. Chemotherapy, immunotherapy, and targeted therapy are permitted when the regimen is stable, treatment-related toxicities are CTCAE Grade 2 or lower, and protocol-specified timing requirements before psilocybin dosing are met. * Opioid analgesic or corticosteroid use that does not meet protocol requirements. Opioids must be on a stable dose for at least 1 week without opioid-induced delirium or clinically significant respiratory compromise. Corticosteroids must generally be stable for at least 2 weeks; high-dose dexamethasone for acute central nervous system edema requires dosing to be deferred until clinically stable.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Trial Feasibility Based on Prespecified RED/YELLOW/GREEN Progression Criteria | From initial referral/screening through the 3-month follow-up (A5), up to approximately 4 months | Overall trial feasibility will be assessed using prespecified progression criteria covering recruitment, intervention delivery, and retention. Component metrics include screening completion among referred individuals, eligibility among screened individuals, enrollment among eligible individuals, preparation-session attendance, integration-session attendance, completion of the 1-week post-dose assessment (A3), and completion of the 3-month follow-up (A5). Each component will be expressed as a proportion and classified according to prespecified RED (review), YELLOW (amend), or GREEN (go) thresholds. The overall feasibility classification will be determined by the worst-performing component, resulting in a single overall RED/YELLOW/GREEN progression classification. Feasibility will be assessed pooled across all four intervention arms. |
| Incidence of Adverse Events (AEs) | From informed consent through the 3-month follow-up (A5), approximately up to 4 months | Safety will be assessed in all participants who receive psilocybin. Adverse events will be collected from informed consent through the 3-month follow-up (A5) and summarized as the number and proportion of participants experiencing one or more adverse events. Events will be characterized by severity, relationship to psilocybin, dose group, and timing. Serious adverse events (SAEs) and protocol-defined adverse events of special interest (AESIs) will be identified and summarized as prespecified safety categories. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Demoralization Scale-II (DS-II) Total Score | Baseline to 1 week post-dose | Demoralization will be assessed using the Demoralization Scale-II (DS-II), a 16-item self-report measure. Each item is scored from 0 to 2, yielding a total score ranging from 0 to 32. Higher scores indicate greater demoralization (a worse outcome). The outcome is the change in DS-II total score from baseline (A1) to 1 week post-dosing (A3). |
| Change in anxiety symptoms assessed by PROMIS Anxiety Short Form 8a | Baseline through 3 months post-dose | Anxiety symptoms will be assessed using the 8-item PROMIS Anxiety Short Form 8a. Change in anxiety will be evaluated from baseline across post-dose follow-up assessments. |
| Change in depressive symptoms assessed by PROMIS Depression Short Form 8a | Baseline through 3 months post-dose | Depressive symptoms will be assessed using the 8-item PROMIS Depression Short Form 8a. Change in depressive symptoms will be evaluated from baseline across post-dose follow-up assessments. |
| Change in Death and Dying Distress Scale (DADDS) Total Score | Baseline through 3 months post-dose | Death and dying distress will be assessed using the 15-item Death and Dying Distress Scale (DADDS). Each item is scored from 0 to 5, yielding a total score ranging from 0 to 75. Higher scores indicate greater death and dying distress and therefore a worse outcome. Change in DADDS total score will be evaluated from baseline across post-dose follow-up assessments. |
| Change in Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being 12-Item Scale (FACIT-Sp-12) Score | Baseline through 3 months post-dose | Spiritual well-being will be assessed using the 12-item Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being scale (FACIT-Sp-12). Change in spiritual well-being will be evaluated from baseline across post-dose follow-up assessments. |
| Change in PROMIS Pain Intensity Score | Baseline through 3 months post-dose | Pain intensity will be assessed using the 3-item PROMIS Pain Intensity measure. Change in pain intensity will be evaluated from baseline across post-dose follow-up assessments. |
| Change in PROMIS Pain Interference Score | Baseline through 3 months post-dose | Pain interference will be assessed using the 4-item PROMIS Pain Interference measure. Change in pain interference will be evaluated from baseline across post-dose follow-up assessments. |
| Change in EuroQol Five-Dimension Five-Level (EQ-5D-5L) Health Utility Score | Baseline through 3 months post-dose | Health-related quality of life will be assessed using the EuroQol Five-Dimension Five-Level Questionnaire (EQ-5D-5L). Responses across the five dimensions will be converted to health-utility values using an appropriate validated value set. Change in health utility will be evaluated across follow-up. |
| Change in Mindfulness Assessed by the Mindful Allowance 8-Item Short Form | Baseline through 3 months post-dose | Mindfulness will be assessed using the Mindful Allowance 8-Item Short Form, a PROMIS-based self-report measure. Change in mindfulness will be evaluated from baseline across post-dose follow-up assessments. Higher scores indicate greater mindful allowance/mindfulness. |
Countries
Canada
Contacts
CONTACTChristopher P. Albertyn, PhD
CONTACTChantal Savard, BA
PRINCIPAL_INVESTIGATORLinda E. Carlson, Ph.D., R.Psych, FCAHS, FABMR
University of Calgary
PRINCIPAL_INVESTIGATORRon Shore, MPA, PhD
Queen's University
PRINCIPAL_INVESTIGATORHarriet Richardson, MSc, PhD
Queen's University
Outcome results
None listed