Advanced CancerPhase 2NCT06416085
Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) Therapy for Patients With Advanced Cancer
A Phase 2 study testing Psilocybin in people with Advanced Cancer and Stage IV Solid Tumor Cancer, run by University Health Network, Toronto at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Cancer, Stage IV Solid Tumor Cancer, Stage IV Sarcoma of Bone
- What is being tested?
- Psilocybin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteCanada
- Study dates
- 6 Jun 2024to 15 Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- >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).
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- 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.
Who cannot join
- 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.
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- 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
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) Therapy for Patients With Advanced Cancer: A Phase II Open-Label Trial
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.
Read the 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.
- Conditions
- Advanced Cancer, Stage IV Solid Tumor Cancer, Stage IV Sarcoma of Bone, Stage IV Lymphoma, Stage IV Melanoma, Endocrine Cancer
- Being tested
- Psilocybin
- Keywords
- Advanced Cancer
- Medical subject headings
- Osteosarcoma, Lymphoma, Melanoma, Endocrine Gland Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PsilocybinDrug
Single high-dose (25mg) capsule of psilocybin taken orally in the context of Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy
| Study group | Role | What they receive |
|---|---|---|
| Psilocybin | Experimental | Not described Receives: Drug: Psilocybin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
The Death and Dying Distress Scale (DADDS) is a 15-item self-report measure designed for populations facing imminent death and addresses fears about the dying process, and about lost opportunities and self-perceived burden placed on others as a result of impending mortality. Total score range is 0 to 75. Higher scores indicate greater death-related distress.
Measured: 24 months
Patient perspectives on the clinical relevance of potential PEARL therapy outcomes: Depressive symptoms as assessed with the PHQ-9.
The Patient Health Questionnaire-9 (PHQ-9) is a 9-item self-report scale measuring depressive symptoms. Total score range is 0 to 27. Higher scores indicate greater severity of depression.
Measured: 24 months
Patient perspectives on the clinical relevance of potential PEARL therapy outcomes: Anxiety symptoms as assessed with the GAD-7.
The Generalized Anxiety Disorder-7 (GAD-7) is a 7-item self-report scale used to screen for and measure anxiety symptoms. Total score range is 0 to 21. Higher scores indicate higher levels of anxiety.
Measured: 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.
The Demoralization Symptoms (DS) is a 24-item self-report measure that assesses loss of meaning and purpose, disheartenment, and helplessness. Total score range is 0 to 96. Higher scores indicate higher levels of demoralization.
Measured: 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.
The Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp) is a 12-item scale designed to measure important aspects of spirituality including sense of meaning in one's life, harmony, peacefulness and a sense of comfort and strength from one's faith. Total score range is 0 to 48. Higher scores indicate higher spiritual well-being.
Measured: 24 months
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.
The Quality of Life at the End of Life-Cancer (QUAL-EC) is a 17-item measure that includes subscales which assess symptom impact, preparation for end of life (i.e., the extent to which the family is prepared and financial plans have been made), relationship with healthcare providers (i.e., the extent to which patients feel informed and are able to participate in decisions about their care) and sense of life completion (i.e., being able to share important things and feel connected to others). For Symptom Control, score range is 3 to 15, with higher scores reflecting greater symptom control; for the Relationship with Healthcare Provider, score range is 5 to 25, with higher scores reflecting a better relationship with healthcare providers; for the Preparation for End-of-Life, score range is 4 to 20, with higher scores reflecting greater preparation for end-of-life; and the for Life Completion, score range is 5 to 25, with higher scores reflecting a greater sense of life completion.
Measured: 24 months
Patient perspectives on the clinical relevance of potential PEARL therapy outcomes: Desire for death in the medically ill as assessed with the SAHD.
The Schedule of Attitudes Toward Hastened Death (SAHD) is a 20-item self-report measure of desire for death in the medically ill. Total score range is 0 to 20. Higher scores indicate greater desire for death.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2024
- Study start6 Jun 2024
- Primary completion15 Dec 2026 (estimated)
- Study completion15 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for Advanced CancerStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sarah Hales, MD, Principal investigator, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06416085
- Sponsor's protocol ID
- PEARL
- Other IDs
- 21-5781
- Status last verified
- Jun 2026
- First submitted
- 14 Jan 2024
- Last updated
- 22 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Albers G, Echteld MA, de Vet HC, Onwuteaka-Philipsen BD, van der Linden MH, Deliens L. Evaluation of quality-of-life measures for use in palliative care: a systematic review. Palliat Med. 2010 Jan;24(1):17-37. doi: 10.1177/0269216309346593. Epub 2009 Oct 20.
PubMed 19843620Breitbart W, Rosenfeld B, Gibson C, Pessin H, Poppito S, Nelson C, Tomarken A, Timm AK, Berg A, Jacobson C, Sorger B, Abbey J, Olden M. Meaning-centered group psychotherapy for patients with advanced cancer: a pilot randomized controlled trial. Psychooncology. 2010 Jan;19(1):21-8. doi: 10.1002/pon.1556.
PubMed 19274623Griffiths RR, Johnson MW, Carducci MA, Umbricht A, Richards WA, Richards BD, Cosimano MP, Klinedinst MA. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J Psychopharmacol. 2016 Dec;30(12):1181-1197. doi: 10.1177/0269881116675513.
PubMed 27909165Grossman CH, Brooker J, Michael N, Kissane D. Death anxiety interventions in patients with advanced cancer: A systematic review. Palliat Med. 2018 Jan;32(1):172-184. doi: 10.1177/0269216317722123. Epub 2017 Aug 8.
PubMed 28786328Kissane DW, Wein S, Love A, Lee XQ, Kee PL, Clarke DM. The Demoralization Scale: a report of its development and preliminary validation. J Palliat Care. 2004 Winter;20(4):269-76.
PubMed 15690829Krause S, Rydall A, Hales S, Rodin G, Lo C. Initial validation of the Death and Dying Distress Scale for the assessment of death anxiety in patients with advanced cancer. J Pain Symptom Manage. 2015 Jan;49(1):126-34. doi: 10.1016/j.jpainsymman.2014.04.012. Epub 2014 May 28.
PubMed 24878066Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001 Sep;16(9):606-13. doi: 10.1046/j.1525-1497.2001.016009606.x.
PubMed 11556941Lo C, Hales S, Zimmermann C, Gagliese L, Rydall A, Rodin G. Measuring death-related anxiety in advanced cancer: preliminary psychometrics of the Death and Dying Distress Scale. J Pediatr Hematol Oncol. 2011 Oct;33 Suppl 2:S140-5. doi: 10.1097/MPH.0b013e318230e1fd.
PubMed 21952572Morita T, Murata H, Kishi E, Miyashita M, Yamaguchi T, Uchitomi Y; Japanese Spiritual Care Task Force. Meaninglessness in terminally ill cancer patients: a randomized controlled study. J Pain Symptom Manage. 2009 Apr;37(4):649-58. doi: 10.1016/j.jpainsymman.2008.04.017. Epub 2008 Oct 1.
PubMed 18834700Rodin G, Lo C, Mikulincer M, Donner A, Gagliese L, Zimmermann C. Pathways to distress: the multiple determinants of depression, hopelessness, and the desire for hastened death in metastatic cancer patients. Soc Sci Med. 2009 Feb;68(3):562-9. doi: 10.1016/j.socscimed.2008.10.037. Epub 2008 Dec 7.
PubMed 19059687Rodin G, Lo C, Rydall A, Shnall J, Malfitano C, Chiu A, Panday T, Watt S, An E, Nissim R, Li M, Zimmermann C, Hales S. Managing Cancer and Living Meaningfully (CALM): A Randomized Controlled Trial of a Psychological Intervention for Patients With Advanced Cancer. J Clin Oncol. 2018 Aug 10;36(23):2422-2432. doi: 10.1200/JCO.2017.77.1097. Epub 2018 Jun 29.
PubMed 29958037Rosenfeld B, Breitbart W, Galietta M, Kaim M, Funesti-Esch J, Pessin H, Nelson CJ, Brescia R. The schedule of attitudes toward hastened death: Measuring desire for death in terminally ill cancer patients. Cancer. 2000 Jun 15;88(12):2868-75. doi: 10.1002/1097-0142(20000615)88:123.0.co;2-k.
PubMed 10870074Smith KA, Harvath TA, Goy ER, Ganzini L. Predictors of pursuit of physician-assisted death. J Pain Symptom Manage. 2015 Mar;49(3):555-61. doi: 10.1016/j.jpainsymman.2014.06.010. Epub 2014 Aug 10.
PubMed 25116913Spitzer RL, Kroenke K, Williams JB, Lowe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006 May 22;166(10):1092-7. doi: 10.1001/archinte.166.10.1092.
PubMed 16717171Steinhauser KE, Clipp EC, Bosworth HB, McNeilly M, Christakis NA, Voils CI, Tulsky JA. Measuring quality of life at the end of life: validation of the QUAL-E. Palliat Support Care. 2004 Mar;2(1):3-14. doi: 10.1017/s1478951504040027.
PubMed 16594230
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) Therapy for Patients With Advanced Cancer: A Phase II Open-Label Trial
- ClinicalTrials.gov ID
- NCT06416085
- Acronym / sponsor ID
- PEARL
- Conditions
- Advanced Cancer, Stage IV Solid Tumor Cancer, Stage IV Sarcoma of Bone, Stage IV Lymphoma, Stage IV Melanoma, Endocrine Cancer
- Keywords
- Advanced Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- 6 Jun 2024 (actual)
- Primary completion
- 15 Dec 2026 (estimated)
- Study completion
- 15 Dec 2026 (estimated)
- First posted
- 16 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Psilocybin | Experimental | Drug: Psilocybin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- >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.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PsilocybinSingle high-dose (25mg) capsule of psilocybin taken orally in the context of Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy | Drug | Psilocybin |
Primary outcome
Recruitment feasibility as assessed by the number of patients who consent/number of patients who meet eligibility criteria.
Time frame: 24 months
Used to assess feasibility of PEARL therapy.
Retention feasibility as assessed by the number of patients completing primary endpoint measures/number of patients consented.
Time frame: 24 months
Used to assess feasibility of PEARL therapy.
Adherence feasibility as assessed by the number of patients completing all PEARL sessions/number of patients consented.
Time frame: 24 months
Used to assess feasibility of PEARL therapy.
Acceptability of PEARL therapy from the perspective of advanced cancer patients obtained through qualitative interviews.
Time frame: 24 months
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.
Safety of PEARL therapy.
Time frame: 24 months
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.
7 secondary outcomes
Patient perspectives on the clinical relevance of potential PEARL therapy outcomes: Death anxiety in advanced cancer patients as assessed with the DADDS.
Time frame: 24 months
Patient perspectives on the clinical relevance of potential PEARL therapy outcomes: Depressive symptoms as assessed with the PHQ-9.
Time frame: 24 months
Patient perspectives on the clinical relevance of potential PEARL therapy outcomes: Anxiety symptoms as assessed with the GAD-7.
Time frame: 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.
Time frame: 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.
Time frame: 24 months
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.
Time frame: 24 months
Patient perspectives on the clinical relevance of potential PEARL therapy outcomes: Desire for death in the medically ill as assessed with the SAHD.
Time frame: 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2026.
- Background: PubMed 19843620Albers G, Echteld MA, de Vet HC, Onwuteaka-Philipsen BD, van der Linden MH, Deliens L. Evaluation of quality-of-life measures for use in palliative care: a systematic review. Palliat Med. 2010 Jan;24(1):17-37. doi: 10.1177/0269216309346593. Epub 2009 Oct 20.
- Background: PubMed 19274623Breitbart W, Rosenfeld B, Gibson C, Pessin H, Poppito S, Nelson C, Tomarken A, Timm AK, Berg A, Jacobson C, Sorger B, Abbey J, Olden M. Meaning-centered group psychotherapy for patients with advanced cancer: a pilot randomized controlled trial. Psychooncology. 2010 Jan;19(1):21-8. doi: 10.1002/pon.1556.
- Background: PubMed 27909165Griffiths RR, Johnson MW, Carducci MA, Umbricht A, Richards WA, Richards BD, Cosimano MP, Klinedinst MA. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J Psychopharmacol. 2016 Dec;30(12):1181-1197. doi: 10.1177/0269881116675513.
- Background: PubMed 28786328Grossman CH, Brooker J, Michael N, Kissane D. Death anxiety interventions in patients with advanced cancer: A systematic review. Palliat Med. 2018 Jan;32(1):172-184. doi: 10.1177/0269216317722123. Epub 2017 Aug 8.
- Background: PubMed 15690829Kissane DW, Wein S, Love A, Lee XQ, Kee PL, Clarke DM. The Demoralization Scale: a report of its development and preliminary validation. J Palliat Care. 2004 Winter;20(4):269-76.
- Background: PubMed 24878066Krause S, Rydall A, Hales S, Rodin G, Lo C. Initial validation of the Death and Dying Distress Scale for the assessment of death anxiety in patients with advanced cancer. J Pain Symptom Manage. 2015 Jan;49(1):126-34. doi: 10.1016/j.jpainsymman.2014.04.012. Epub 2014 May 28.
- Background: PubMed 11556941Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001 Sep;16(9):606-13. doi: 10.1046/j.1525-1497.2001.016009606.x.
- Background: PubMed 21952572Lo C, Hales S, Zimmermann C, Gagliese L, Rydall A, Rodin G. Measuring death-related anxiety in advanced cancer: preliminary psychometrics of the Death and Dying Distress Scale. J Pediatr Hematol Oncol. 2011 Oct;33 Suppl 2:S140-5. doi: 10.1097/MPH.0b013e318230e1fd.
- Background: PubMed 18834700Morita T, Murata H, Kishi E, Miyashita M, Yamaguchi T, Uchitomi Y; Japanese Spiritual Care Task Force. Meaninglessness in terminally ill cancer patients: a randomized controlled study. J Pain Symptom Manage. 2009 Apr;37(4):649-58. doi: 10.1016/j.jpainsymman.2008.04.017. Epub 2008 Oct 1.
- Background: PubMed 19059687Rodin G, Lo C, Mikulincer M, Donner A, Gagliese L, Zimmermann C. Pathways to distress: the multiple determinants of depression, hopelessness, and the desire for hastened death in metastatic cancer patients. Soc Sci Med. 2009 Feb;68(3):562-9. doi: 10.1016/j.socscimed.2008.10.037. Epub 2008 Dec 7.
- Background: PubMed 29958037Rodin G, Lo C, Rydall A, Shnall J, Malfitano C, Chiu A, Panday T, Watt S, An E, Nissim R, Li M, Zimmermann C, Hales S. Managing Cancer and Living Meaningfully (CALM): A Randomized Controlled Trial of a Psychological Intervention for Patients With Advanced Cancer. J Clin Oncol. 2018 Aug 10;36(23):2422-2432. doi: 10.1200/JCO.2017.77.1097. Epub 2018 Jun 29.
- Background: PubMed 10870074Rosenfeld B, Breitbart W, Galietta M, Kaim M, Funesti-Esch J, Pessin H, Nelson CJ, Brescia R. The schedule of attitudes toward hastened death: Measuring desire for death in terminally ill cancer patients. Cancer. 2000 Jun 15;88(12):2868-75. doi: 10.1002/1097-0142(20000615)88:123.0.co;2-k.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sarah Hales, MD principal investigator
University Health Network, Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Psilocybin in people with Advanced Cancer and Stage IV Solid Tumor Cancer, run by University Health Network, Toronto at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 22 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recruitment feasibility as assessed by the number of patients who consent/number of patients who meet eligibility criteria. (time frame: 24 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06416085, which also lists 16 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2026.