Clinical trial NCT06416085: Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) Therapy for Patients With Advanced Cancer
Official title: Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) Therapy for Patients With Advanced Cancer: A Phase II Open-Label Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Advanced Cancer
Stage IV Solid Tumor Cancer
Stage IV Sarcoma of Bone
Stage IV Lymphoma
Stage IV Melanoma
Endocrine Cancer
Keywords: Advanced Cancer
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2024-05-16
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: The PEARL Pilot is a phase II open-label trial. Participants will receive a single high-dose (25 mg) of psilocybin in the context of Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy.

Detailed description: Individuals with advanced cancer often experience high levels of distress due to physical suffering, difficult treatment decisions, social isolation, and fear of death. While there are many treatment options for the management of physical symptoms associated with cancer, there are relatively few standard treatment approaches to help patients deal with psychological and existential suffering. Over the past decade, research has shown that psychotherapies incorporating existential, attachment and relational approaches can address the specific needs and challenges of the advanced cancer population and thus help to reduce distress. Simultaneously, recent research has shown that psilocybin-assisted psychotherapy, in which, an individual ingests the psychoactive drug within the carefully monitored therapeutic setting, can reduce end-of-life distress and greatly benefit those with advanced disease. The multidisciplinary team has combined these two evidence-based approaches into what the team calls Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy. PEARL therapy combines elements from psilocybin-assisted psychotherapy, including preparatory therapy sessions, a high-dose drug session, and integration sessions, with important elements from manualized individual psychotherapies designed for patients with advanced cancer. This study will assess the feasibility, acceptability, and safety of PEARL therapy among patients with advanced cancer. This study will yield important information about the feasibility of this type of therapy and contribute to the growing research around the efficacy of psychedelic-assisted therapies. This type of therapy has the potential to improve quality of life among those with advanced disease and careful research is needed to build upon previous findings to outline the necessary components of therapy and guide public policy, legislation, and clinical guidelines.

Eligibility criteria: Inclusion Criteria:

1. \>18 years of age.
2. Ability to speak and read English (patient to provide written informed consent and participate in PEARL intervention, as determined by study personnel).
3. Resident of Ontario.
4. No cognitive impairment indicated in medical record or by attending oncologist or palliative care physician.
5. Confirmed diagnosis of stage IV solid tumour cancers, sarcoma, endocrine, melanoma cancers, or stage 4 lymphoma with expected survival of greater than 6 months as determined by their oncologist or palliative care physician.
6. At least mild depressive symptoms, defined as \>8 on the Patient Health Questionnaire-9 (PHQ-9) (Kroenke et la., 2001).
7. Interest in and ability to participate in and complete the PEARL intervention and protocol as outlined.
8. Participants who are sexually active and could become pregnant must be using effective birth control (per their physician), prior to study entry, during study participation, and for the duration of the study. Participants who are sexually active and could inseminate a partner must agree to use effective birth control after psilocybin administration until the end of study. For participants of child-bearing potential, a negative serum pregnancy test result is required at screening. A urine pregnancy test will be administered on the morning of psilocybin administration for applicable participants. Participants cannot be pregnant or nursing through the duration of the study.
9. If using prescribed medications or other substances, participants must agree to refrain from taking them if instructed by study investigators. These include:

   * not using any non-prescription medication, nutritional supplement, or herbal supplement except when approved by the treatment team (exceptions will be evaluated by the Investigator and will include acetaminophen, non-steroidal anti-inflammatory drugs, and common doses of vitamins and minerals),
   * not using nicotine for at least 2 hours before psilocybin administration, and not again until approximately 7 hours after psilocybin administration,
   * consuming approximately the same amount of caffeine-containing beverages (e.g., coffee, tea) that they consume on a usual morning before arriving at the treatment centre for the psilocybin session day,
   * not taking any as needed medications on the mornings of psilocybin sessions (with the exception of daily and as needed opioid pain medication),
   * refraining from using any psychoactive drugs, including alcoholic beverages, within 24 hours of the psilocybin administration.
10. Participants must have someone drive them after the session to where they are staying (home, hotel or another location), because psilocybin may affect their alertness and concentration on the evening of the dosing session.

Exclusion Criteria:

1. Primary cancer of the brain, or metastasis to the brain associated with clinically significant symptoms (e.g., affective, cognitive, personality-related, psychotic, or other symptoms, including seizures).
2. Symptoms consistent with delirium, psychosis, or other symptoms judged to be incompatible with establishment of rapport or safe exposure to psilocybin.
3. A history of past intolerability of psilocybin or other psychedelics.
4. Past/present psychiatric diagnoses including bipolar disorder, psychotic disorders, active substance use disorders or suicidality (as distinguished from desire for hastened death or readiness for death, per the discretion of the study team).
5. If participant is under 30 years of age and has first degree relative with a primary psychotic disorder.
6. Severe hypertension (defined as systolic blood pressure \>150/or diastolic pressure \>95) based on two readings on the same day. If the second reading remains over 150/95, the patient can be brought in for another reading on a different day. Patients can be re-screened for participation once blood pressure is adequately controlled.
7. Moderate or severe hepatic impairment, as defined by Child-Pugh class B or C, or elevations in AST or ALT greater than 3 times the upper limit of normal.
8. Severe renal impairment (defined as eGFR \< 30).
9. Known paraneoplastic syndrome or "ectopic" hormone production by the primary tumor if incompatible with psilocybin, determined in consultation with the study palliative care physician. Patients could be enrolled if it is determined that the patient's condition is compatible with psilocybin administration.
10. Cardiovascular conditions including uncontrolled hypertension, angina, a clinically significant ECG abnormality (e.g., atrial fibrillation without rate control), transient ischemic attack in the last six months, stroke, peripheral or pulmonary vascular disease (no active claudication).
11. Uncontrolled epilepsy or history of seizures in past 6 months.
12. Participants with diabetes who are unable to skip a meal (lunch), or whose diabetes requires administration of medication more than twice daily, or who have had symptomatic hypoglycemia within the prior 30 days.
13. GI bleed in last 6 months.
14. Use of other agents that would be inappropriate to take with psilocybin in the judgement of the investigator. These agents may include psychoactive prescription medications (e.g., benzodiazepines, lithium, Selective serotonin reuptake inhibitors), medications having a primary pharmacological effect on serotonin-2a (5-HT2A) receptors (e.g., olanzapine), or medications that are monoamine oxidase (MAO) inhibitors, any potent metabolic inducers (e.g. rifamycin, rifampin, rifabutin, rifapentine, carbamazepine, phenytoin, phenobarbital, nevirapine, efavirenz, taxol, dexamethasone, St John's wort) or inhibitors (e.g. HIV protease inhibitors, itraconazole, ketoconazole, erythromycin, clarithromycin, troleandomycin).

Of note, in suitable patients, these medications may be paused or tapered between study enrolment and prior to the start of the intervention when it is deemed safe to do so. A safe and appropriate tapering regimen will then be developed based on the particular medication, on a case-by-case basis. If taking an MAO inhibitor, the psilocybin session will not be conducted until at least 5 half-lives of the agent have elapsed after the last dose. Patients prescribed opioids will be allowed to take their usual dose regimen for analgesia, including the use of as needed analgesic medications on psilocybin session days.

Primary outcomes:
measure: Recruitment feasibility as assessed by the number of patients who consent/number of patients who meet eligibility criteria.
timeFrame: 24 months
measure: Retention feasibility as assessed by the number of patients completing primary endpoint measures/number of patients consented.
timeFrame: 24 months
measure: Adherence feasibility as assessed by the number of patients completing all PEARL sessions/number of patients consented.
timeFrame: 24 months
measure: Acceptability of PEARL therapy from the perspective of advanced cancer patients obtained through qualitative interviews.
timeFrame: 24 months
measure: Safety of PEARL therapy.
timeFrame: 24 months
Secondary outcomes:
measure: Patient perspectives on the clinical relevance of potential PEARL therapy outcomes: Death anxiety in advanced cancer patients as assessed with the DADDS.
timeFrame: 24 months
measure: Patient perspectives on the clinical relevance of potential PEARL therapy outcomes: Depressive symptoms as assessed with the PHQ-9.
timeFrame: 24 months
measure: Patient perspectives on the clinical relevance of potential PEARL therapy outcomes: Anxiety symptoms as assessed with the GAD-7.
timeFrame: 24 months
measure: Patient perspectives on the clinical relevance of potential PEARL therapy outcomes: Loss of meaning and purpose, disheartenment and helplessness as assessed with the DS.
timeFrame: 24 months
measure: Patient perspectives on the clinical relevance of potential PEARL therapy outcomes: Overall measure of spiritual well-being, meaning/peace and faith as assessed with the FACIT-Sp.
timeFrame: 24 months
measure: Patient perspectives on the clinical relevance of potential PEARL therapy outcomes: Broad quality of life construct in patients facing end of life as assessed with the QUAL-EC.
timeFrame: 24 months
measure: Patient perspectives on the clinical relevance of potential PEARL therapy outcomes: Desire for death in the medically ill as assessed with the SAHD.
timeFrame: 24 months
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Sarah Hales, MD
role: PRINCIPAL_INVESTIGATOR
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