Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) Therapy for Patients With Advanced Cancer

NCT06416085 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: PEARL21-5781
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced Cancer; Stage IV Solid Tumor Cancer; Stage IV Sarcoma of Bone; Endocrine Cancer; Stage IV Lymphoma; Stage IV Melanoma

Keywords

Advanced Cancer

Outcome Measures

Primary Outcomes (5)

• Recruitment feasibility as assessed by the number of patients who consent/number of patients who meet eligibility criteria.

  Used to assess feasibility of PEARL therapy.

  24 months

• Retention feasibility as assessed by the number of patients completing primary endpoint measures/number of patients consented.

  Used to assess feasibility of PEARL therapy.

  24 months

• Adherence feasibility as assessed by the number of patients completing all PEARL sessions/number of patients consented.

  Used to assess feasibility of PEARL therapy.

  24 months

• Acceptability of PEARL therapy from the perspective of advanced cancer patients obtained through qualitative interviews.

  Participants will be interviewed regarding their experiences with PEARL, including acceptability and perceived positive and negative effects of the intervention, with a semi-structured interview guide.

  24 months

• Safety of PEARL therapy.

  Safety will be assessed throughout the trial. Adverse events (AEs) attributed to psilocybin will be monitored for and recorded after the psilocybin session. This study will use CTCAE v5.0 to assess AEs. Serious adverse events (SAEs) will be tracked until study completion and will be defined as any adverse drug experience that: results in death; that is life-threatening (i.e. any AE that places the participant, in the view of the investigators, at immediate risk of death from the reaction as it occurs); requires hospital admission; results in persistent or significant disability (i.e. a substantial disruption of a person's ability to conduct normal life functions); or may jeopardize the participant or necessitate medical intervention to prevent one of the aforementioned criteria.

  24 months

Secondary Outcomes (7)

• Patient perspectives on the clinical relevance of potential PEARL therapy outcomes: Death anxiety in advanced cancer patients as assessed with the DADDS.

  24 months

• Patient perspectives on the clinical relevance of potential PEARL therapy outcomes: Depressive symptoms as assessed with the PHQ-9.

  24 months

• Patient perspectives on the clinical relevance of potential PEARL therapy outcomes: Anxiety symptoms as assessed with the GAD-7.

  24 months

• Patient perspectives on the clinical relevance of potential PEARL therapy outcomes: Loss of meaning and purpose, disheartenment and helplessness as assessed with the DS.

  24 months

• 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.

  24 months

Study Arms (1)

Psilocybin

EXPERIMENTAL

Drug: Psilocybin

Interventions

Psilocybin DRUG

Single high-dose (25mg) capsule of psilocybin taken orally in the context of Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy

Psilocybin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \>18 years of age.
• Ability to speak and read English (patient to provide written informed consent and participate in PEARL intervention, as determined by study personnel).
• Resident of Ontario.
• No cognitive impairment indicated in medical record or by attending oncologist or palliative care physician.
• 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.
• At least mild depressive symptoms, defined as \>8 on the Patient Health Questionnaire-9 (PHQ-9) (Kroenke et la., 2001).
• Interest in and ability to participate in and complete the PEARL intervention and protocol as outlined.
• 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.
• 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.
• 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.

You may not qualify if:

• 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).
• Symptoms consistent with delirium, psychosis, or other symptoms judged to be incompatible with establishment of rapport or safe exposure to psilocybin.
• A history of past intolerability of psilocybin or other psychedelics.
• Past/present psychiatric diagnoses including bipolar I 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).
• If participant is under 30 years of age and has first degree relative with a primary psychotic disorder.
• 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.
• 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.
• Severe renal impairment (defined as eGFR \< 30).
• 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.
• 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).
• Uncontrolled epilepsy or history of seizures in past 6 months.
• 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.
• GI bleed in last 6 months.
• 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).
• Any other medical condition or laboratory abnormality judged to be incompatible with safe exposure to psilocybin

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (16)

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• Richardson C, Chan C, Macgregor E, Hare C, Hannon B, Black S, Schneider E, Buchman D, Wang S, Rac V, Abrahamyan L, Huszti E, Nissim R, Li M, Zimmermann C, Hapke E, Rosenbaum D, Hales S. Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy for patients with advanced cancer: protocol for a multi-method feasibility trial. Pilot Feasibility Stud. 2025 Oct 28;11(1):126. doi: 10.1186/s40814-025-01706-5.

  PMID: 41152967 DERIVED

MeSH Terms

Conditions

Osteosarcoma; Lymphoma; Melanoma; Endocrine Gland Neoplasms

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Officials

• Sarah Hales, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2024
• First Posted: May 16, 2024
• Study Start: June 6, 2024
• Primary Completion (Estimated): December 15, 2026
• Study Completion (Estimated): December 15, 2026
• Last Updated: March 5, 2026

Record last verified: 2026-03

Locations

CA (1)