Psilocybin-Assisted Therapy for the Treatment of Cancer-Related Anxiety in Patients With Metastatic Cancer

Study Overview
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Brief Summary
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This phase I/II trial tests the safety and side effects of psilocybin in combination with therapy for the treatment of patients with metastatic cancer and symptoms of anxiety and/or depression. Psilocybin is a substance being studied in conjunction with therapy for the treatment of anxiety and depression in patients with cancer. In this study, the psilocybin being used is derived from the mushroom psilocybe cubensis using a patented process that results in a pharmaceutical grade version of psilocybin. Psilocybin acts by activating serotonin receptors on brain cells which can change perceptions and patterns of thinking in ways that may decrease anxiety.

Detailed Description
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OUTLINE: Patients receive psilocybin orally (PO) and participate in group and individual therapy sessions on trial.

Official Title
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A Phase 1/2 Study of a Group Model of Psilocybin-Assisted Therapy for Cancer-Related Anxiety in Patients With Metastatic Cancer

Conditions
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Hematopoietic and Lymphoid System Neoplasm, Metastatic Malignant Solid Neoplasm

Intervention / Treatment
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* Other: Counseling
* Drug: Psilocybin
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A diagnosis of metastatic solid tumor, or incurable hematologic malignancy that has been accepted by a physician in a medical record Measurable disease is not required Previous treatment with chemotherapy: There are no minimum or maximum prior lines of chemotherapy 18-80 years of age Required performance status, including the appropriate scale. Eastern Cooperative Oncology Group (ECOG) 0-2 Hematocrit > 20 Platelets (Plt) > 20K Liver function tests 1.5 x normal Creatinine 1.5 x normal Subjects of childbearing potential must be willing to use an effective contraceptive method from study enrollment until at least 1 month after receiving the investigational agent(s) Must be at least 4 weeks after surgery or radiotherapy at study entry, but can be receiving oral or iv chemotherapy if those schedules can be adjusted around the medication session date Motivated to participate in a group study and able in the research team's judgment to participate in the small group effectively On pre-enrollment screening tests, they will have clinically significant anxiety or depressive symptoms as defined by a score of 11 or greater on the Hospital Anxiety and Depression Scale (HADS)-Total English speaking- able to understand the process of consent and the risk and benefits associated with the study, and able to give written informed consent. This is a pilot study, and if future larger studies are designed, consideration will be given for non-English-speaking subjects Must be willing to sign a medical release for the investigators to communicate directly with their treating clinicians (mental health professional or oncologist) and doctors to confirm a medication and/or medical history Must provide at least one adult who is in contact with the participant at least once a day when the participant is at home who is able to verbally monitor participant-reported changes in the behavior and able to notify research staff of behavior changes that may require research staff assessment Has been off selective serotonin inhibitors for five half-lives of the drug plus 2 weeks Must avoid taking any psychiatric medications or starting a new psychiatric medication during the study. Should participant's doctor recommend starting a new psychiatric medication, participant will be required to notify the study team and the subject would withdraw from the study. (Use of prn benzodiazepines is allowed but high dose chronic benzodiazepine use must be reviewed by the principal investigator [PI]. Use of as needed [prn] gabapentoids is allowed by high dose chronic gabapentoid use must be reviewed by the PI) Must provide a contact (relative, spouse, close friend, or other caregiver; can be the same person) who is willing and able to be reached by the research team in the event that the participant becomes suicidal If the potential participant is of childbearing potential, they must have a negative pregnancy test at baseline and prior to the medication dosing session, and must agree to use adequate birth control Are willing to commit to preparation sessions, medication dosing sessions, integration sessions, to complete evaluation instruments and commit to be contacted for all necessary telephone contacts Exclusion Criteria: Brain metastases that have not been treated Uncontrolled or concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Pregnancy, breastfeeding, or expecting to conceive or father children for the duration of the trial through 30 days after receipt of investigational agent(s) Personal or immediate family history of schizophrenia, bipolar affective disorder, delusion disorder, paranoid disorder, or schizoaffective disorder Suicidal ideation with a Columbia-Suicidality Severity Rating Scale (C-SSRS) >= 3 Current substance abuse disorder (although prospective subjects will not be excluded for reasonable alcohol use that does not meet criteria for alcohol use disorder or marijuana use that does not meet criteria for substance use disorder) Neuroleptic (including olanzapine, prochlorperazine, promethazine), and selective serotonin reuptake inhibitor (SSRI) medications that cannot be tapered and discontinued in conjunction with the participant's prescribing physician (although ondansetron can be used for nausea) Unstable neurological or medical condition; history of seizure, chronic/severe headaches Any use of psychedelic drugs in high doses (psilocybin > 2 grams of dried mushrooms, LSD > 200 micrograms) within the prior 12 months (microdosing will not require exclusion but participants would have to agree to discontinue microdosing 1 month before study entry) Use of tramadol, due to the potential for serotonin syndrome with concomitant use of psilocybin Individuals who are on MOAI (monoamine oxidase inhibitors) or who have a known sensitivity to the drug or its metabolites. Psilocybin is contraindicated in medications that are known UGT (UDP-glucuronosyltransferase) enzyme modulators. The concurrent use of SSRI/serotonin-norepinephrine reuptake inhibitor (SNRI) meds is assumed to be contraindicated due to the potential to increase the risk of serotonin syndrome and/or to attenuate the binding of psilocin to the HT2A receptor A marked baseline prolongation of QT/corrected QT (QTc) interval (e.g., demonstration on > 1 electrocardiogram (ECG) of a QTc interval > 450 milliseconds (ms) A history of additional risk factors for Torsade de Points (including but not limited to: heart failure, hypokalemia, family history of long QT syndrome) The use of concomitant medications that prolong the QT/QTc interval

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (psilocybin, therapy)<br>Patients receive psilocybin PO and participate in group and individual therapy sessions on trial. | Other: Counseling<br>* Participate in therapy visits<br>* Other names: Counseling Intervention;Drug: Psilocybin<br>* Given PO<br>* Other names: psilocybine;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 |
| --- | --- | --- |
| Number of instances of potentially unattended psilocybin-related distress during psilocybin sessions. | Defined as the occurrence of participant distress among study participants in the small group during the psilocybin administration session on Day 0 that requires 1:1 facilitator attention that cannot be met by the 4-person facilitation team. The size of small groups of different sizes will vary over the course of the study. Descriptive statistics will be used to analyze and will be tabulated after each group intervention (which will happen approximately every month). Backup facilitators will be available when this occurs. | At psilocybin administration session on day 0 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in measured anxiety and depression: Hospital Anxiety and Depression Scale (HADS) | The Hospital Anxiety and Depression Scale (HADS) is a self-administered measure of depression and anxiety. The HADS is not a diagnostic tool, but can screen for anxiety and depression. The HADS has 14 items in total and asks about mood in the past week. Seven items assess depression and seven items assess anxiety. The HADS can be administered repeatedly without impacting on validity. Each item is rated on a 4-point scale and provide a score 0-21. A higher score indicates higher distress. | From 14 days before the psilocybin session to 28 days (4 weeks) after the psilocybin session |