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

Last updated: July 15, 2024
Sponsor: University Health Network, Toronto
Overall Status: Active - Recruiting

Phase

2

Condition

Neoplasms

Metastatic Melanoma

Metastatic Cancer

Treatment

Psilocybin

Clinical Study ID

NCT06416085
PEARL
21-5781
  • Ages > 18
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. >18 years of age;

  2. Ability to speak and read English (patient to provide written informed consent andparticipate in PEARL intervention, as determined by study personnel);

  3. No cognitive impairment indicated in medical record or by attending oncologist orpalliative care physician;

  4. Confirmed diagnosis of stage IV solid tumour cancers, sarcoma, endocrine, melanomacancers, or stage 4 lymphoma with expected survival of greater than 6 months asdetermined by their oncologist or palliative care physician;

  5. At least mild depressive symptoms, defined as >8 on the Patient HealthQuestionnaire-9 (PHQ-9) (Kroenke et la., 2001);

  6. Interest in and ability to participate in and complete the PEARL intervention andprotocol as outlined;

  7. Normal hepatic functioning as determined by prior medical history or/and screeningbloodwork (INR<1.5, Aspartate aminotransferase/Alanine Aminotransferase (AST/ALT) < 2x upper limit of normal, normal range bilirubin, platelets > 150)

  8. Normal renal functioning as determined by prior medical history or/and screeningbloodwork (eGFR>45)

  9. Participants who are sexually active and could become pregnant must be usingeffective birth control (per their physician), prior to study entry, during studyparticipation, and for the duration of the study. Participants who are sexuallyactive and could inseminate a partner must agree to use effective birth controlafter psilocybin administration until the end of study. For participants ofchild-bearing potential, a negative serum pregnancy test result is required atscreening. A urine pregnancy test will be administered on the morning of psilocybinadministration for applicable participants. Participants cannot be pregnant ornursing through the duration of the study;

  10. If using prescribed medications or other substances, participants must agree torefrain from taking them if instructed by study investigators. These include:

  • not using any non-prescription medication, nutritional supplement, or herbalsupplement except when approved by the treatment team (exceptions will beevaluated by the Investigator and will include acetaminophen, non-steroidalanti-inflammatory drugs, and common doses of vitamins and minerals),

  • not using nicotine for at least 2 hours before psilocybin administration, andnot 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 thetreatment 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.

  1. Participants must have someone drive them after the session to where they arestaying (home, hotel or another location), because psilocybin may affect theiralertness and concentration on the evening of the dosing session.

Exclusion

Exclusion Criteria:

  1. Cancer of the brain or metastasis to the brain;

  2. Symptoms consistent with delirium, psychosis, or other symptoms judged to beincompatible 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 forhastened 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 primarypsychotic disorder;

  6. Severe hypertension (defined as systolic blood pressure >140/or diastolic pressure >90) based on two readings on the same day. If the second reading remains over 140/90 patient can be brought in for another reading on a different day. Patientscan be re-screened for participation once blood pressure is adequately controlled;

  7. Known paraneoplastic syndrome or "ectopic" hormone production by the primary tumorif incompatible with psilocybin, determined in consultation with the studypalliative care physician. Patients could be enrolled if it is determined that thepatient's condition is compatible with psilocybin administration.

  8. Cardiovascular conditions including uncontrolled hypertension, angina, a clinicallysignificant ECG abnormality (e.g., atrial fibrillation without rate control),transient ischemic attack in the last six months, stroke, peripheral or pulmonaryvascular disease (no active claudication);

  9. Uncontrolled epilepsy or history of seizures in past 6 months;

  10. Participants with diabetes who are unable to skip a meal (lunch), or whose diabetesrequires administration of medication more than twice daily, or who have hadsymptomatic hypoglycemia within the prior 30 days

  11. GI bleed in last 6 months;

  12. Use of other agents that would be inappropriate to take with psilocybin in thejudgement of the investigator. These agents may include psychoactive prescriptionmedications (e.g., benzodiazepines, lithium, Selective serotonin reuptakeinhibitors), 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 proteaseinhibitors, 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.

Study Design

Total Participants: 15
Treatment Group(s): 1
Primary Treatment: Psilocybin
Phase: 2
Study Start date:
June 06, 2024
Estimated Completion Date:
June 15, 2026

Study 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.

Connect with a study center

  • Princess Margaret Cancer Centre

    Toronto, Ontario M5G 2M9
    Canada

    Active - Recruiting

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