Psilocybin Combined With Multidisciplinary Palliative Care in Demoralized Cancer Survivors With Chronic Pain

Study Overview
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Brief Summary
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This phase I trial evaluates the side effects of psilocybin and how well it works under supportive care conditions in cancer survivors living with demoralization and chronic pain. Cancer patients often experience demoralization, which is characterized by feelings of hopelessness, loss of meaning, and existential distress. Psilocybin psychotherapy, together with multidisciplinary palliative and supportive care, may help treat the anxiety, depression, and chronic pain felt by cancer survivors - defined here as cancer patients from time of diagnosis through the end-of-life.

Detailed Description
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PRIMARY OBJECTIVE: I. To determine the safety, feasibility, and acceptability of a single administration of 25 mg psilocybin (psilocybin) provided under supportive conditions with multidisciplinary palliative care support (P-PC) in adult cancer survivors living with concurrent demoralization and chronic pain. EXPLORATORY OBJECTIVE: I. To evaluate for changes in demoralization, anxiety, depression, quality of life, pain, other symptoms, mysticism, awe, post-traumatic growth, social isolation, and psychosocial functioning from baseline to end-of-treatment to 3.5-month follow up. OUTLINE: Patients receive psilocybin orally (PO) and undergo observation for up to 8 hours on day 14. After completion of study intervention, patients are followed up on days 15, 21, 42, 56, and 98.

Official Title
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The Safety, Feasibility, and Acceptability of Psilocybin Combined With Multidisciplinary Palliative Care in Demoralized Cancer Survivors With Chronic Pain (P-PC)

Conditions
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Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm

Intervention / Treatment
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* Drug: Psilocybin
* Behavioral: Psychotherapy
* Other: Quality-of-Life Assessment
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent form (ICF) Diagnosis of solid or liquid cancer made >= 1 year at any stage in cancer survivorship (specifically, active cancer treatment or no cancer-directed therapy either in clinical remission or with advanced disease) Prognosis of greater than six months as determined by their primary oncologist Moderate-to-severe demoralization (score of >= 10 on the Demoralization Scale-II [DS-II]) Chronic pain (pain lasting > 3 months) per patient report and score of >= 5 for average pain level on Brief Pain Inventory Age >= 26 years old and ≤85 years old Availability of a friend or family member into whose care the participant can be released following the drug administration session Exclusion Criteria: Pregnancy or breastfeeding Women of childbearing potential (i.e., not permanently sterilized, not postmenopausal) who decline to use a highly effective dual contraceptive method for the duration of the study. Dual contraceptive method use is defined by a use a barrier contraceptive in addition to another method to prevent pregnancy, including sterilization, hormonal methods, intrauterine devices, and hormonal pills. Age < 26 years old and > 85 years old Poor functional status (Eastern Cooperative Oncology Group [ECOG] score of >= 2) Major cognitive impairment as determined by principal investigator Non-fluency in the English language Personal history of a psychotic disorder or Bipolar disorder type I/II Active suicidal ideation with intent in the last 3 months (Columbia Suicide Severity Rating Scale suicidal ideation score > 3) or any suicide attempt in the past year Current substance use disorder (i.e., present in last six months), of greater than mild severity as defined by Diagnostic and Statistical Manual of Mental Disorders (DSM-V) History of a seizure disorder in adulthood Active central nervous system (CNS) metastases or symptomatic CNS infection Uncontrolled hypertension (mean blood pressure (mmHg) exceeding 139 systolic and 89 diastolic) and heart rate exceeding 90 beats per minute Clinically significant cardiovascular disease (coronary artery disease, congestive heart failure, arrhythmia, or QTc>450ms) Supplemental oxygen requirement Body mass index =< 18 Renal insufficiency as evidenced by creatinine clearance (CrCl) < 30 mL/min Concomitant use of drugs known to interact with psilocybin (probenecid, diclofenac) Consistent use of serotonergic drugs including selective serotonin reuptake inhibitors (SSRIs), serotoninnorepinephrine reuptake inhibitors (SNRIs), or efavirenz, as well as monoamine oxidase inhibitors (MAOIs). Subjects using any other antidepressant, stimulant, or antipsychotic medications on Day 0 (baseline visit) may be allowed to enroll in the study if they elect to taper off the medications under medical supervision by the PI and the study psycho-oncologist (PO) by the day prior to the baseline visit Considered by the principal investigator to be inappropriate for the study due to safety concerns or to be unlikely to complete the protocol

Ages Eligible for Study
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Minimum Age: 26 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Supportive care (psilocybin, observation)<br>Patients receive psilocybin PO and undergo observation for up to 24 hours on day 14. | Drug: Psilocybin<br>* Given PO<br>* Other names: Indocybin;Behavioral: Psychotherapy<br>* supportive care<br>* Other names: talk therapy;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence Of Treatment-Related Medical Grade 3 Or Higher Or Psychiatric Grade 4 Or Higher | Adverse events are graded according to Common Terminology Criteria for Adverse Events. Descriptive statistics will summarize the incidence and duration of adverse events, with the primary outcome of interest being the incidence of medical Grade 3 or higher or psychiatric Grade 4 or higher Common Terminology Criteria for Adverse Events considered by the PI to be treatment-related occurring by day 42. These events will be evaluated by adverse events, vital signs, ECG, and laboratory findings. A successful outcome is no medical or psychiatric Grade 4 adverse events or higher. | Up to 42 days | 
| Evaluation of Feasibility Outcome To Assess Patient Retention in The Study | Feasibility will be assessed by patient retention in the study, number of missed events, a survey assessing acceptability of the protocol at study endpoint, and fidelity to the intervention elements. A successful outcome is retention of 80% of subjects enrolled in the study, 80% of events attended by subjects, and 60% of subjects find intervention satisfactory. | Up to 42 days |