Advanced Cancer, Endocrine Cancer, Stage IV Lymphoma, Stage IV Melanoma, Stage IV Sarcoma of Bone, Stage IV Solid Tumor Cancer
Conditions
Brief summary
Phase II randomized controlled trial, followed by an open-label extension phase. In the main study, participants will receive either a single high-dose (25 mg) or low-dose (1 mg) of psilocybin in the context of Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy. Upon completion of main study, participants who received the low dose will be offered to receive a single high-dose of psilocybin (25 mg) in the context of PEARL therapy (Open label extension study).
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 determine if PEARL therapy with 25mg of psilocybin is associated with greater improvement in depressive symptoms when compared to control 2 weeks after treatment completion. Participants will receive either a single high-dose (25 mg) or low-dose (1 mg) of psilocybin in the context of Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy. Upon completion of main study, participants who received low-dose will be offered to receive a single high-dose of psilocybin (25 mg) in the context of PEARL therapy (Open label expansion study). 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.
Interventions
DRUGPsilocybin (25mg)
Single high-dose (25mg) capsule of psilocybin taken orally in the context of Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy
DRUGPsilocybin (1mg)
Single low-dose (1mg) capsule of psilocybin taken orally in the context of Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy
OTHERPEARL Therapy
Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy
Sponsors
University Health Network, Toronto
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Single high-dose (25mg) capsule of psilocybin or low-dose comparator (1mg capsule of psilocybin- control arm) taken orally in the context of Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. \>/= 18 years of age 2. Ability to speak and read English fluently (participant 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 cancer, 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 at the time of screening, defined as a score \>/= 10 on the Montgomery-Asperg Depression Rating Scale (MADRS) Note: Participants may be asked to retake the MADRS if they initially score under 10. 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 or inseminate a partner must be using one method of highly effective contraception (hormonal contraceptives (e.g. combined oral contraceptives, patch, vaginal ring, injectables, and implants); intrauterine device (IUD) or intrauterine system (IUS); vasectomy or tubal ligation). Alternatively, they may use a combination of two or more effective methods of contraception which include male condom, female condom, cervical cap, diaphragm, or contraceptive sponge. These acceptable methods of contraception must be used from the time of informed consent until 28 days after psilocybin administration. 9. 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 10. 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 number 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 11. Participants must have someone drive them after the session to where they are staying (home, hotel or another location), since psilocybin may affect their alertness and concentration on the evening of the dosing session. 12. Participants must agree not to drive or operate machinery for at least 24 hours after dose administration
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 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); 5. If participant is under 30 years of age, 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 (measured during the screening period); if the second reading remains over 150/95, the participant can be brought in for another reading on a different day. Participants 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, as determined in consultation with the study palliative care physician; participants could be enrolled if it is determined that their 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. If participant has diabetes, inability to skip a meal (lunch), or required administration of medication more than twice daily, or symptomatic hypoglycemia within 30 days prior to screening 13. Gastrointestinal bleed in the 6 months prior to screening 14. Use of other agents that would be inappropriate to take with psilocybin in the judgment of the investigator. These agents may include psychoactive prescription medications (e.g., benzodiazepines, lithium, SSRIs), medications having a primary pharmacological effect on serotonin-2a (5-HT2A) receptors (e.g., olanzapine), 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) 15. Any other medication condition or lab abnormality judged to be incompatible with safe exposure to psilocybin.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in mean severity of depressive symptoms as assessed by the Montgomery-Asperg Depression Rating Scale (MADRS) score from baseline to 2 weeks after completion of PEARL therapy, comparing the 25mg psilocybin group with the 1mg psilocybin group. | At T2 (2 weeks after the last follow up) | The MADRS is a 10-item rater-administered scale measuring depressive symptoms. Total score range is 0 to 60, with higher scores indicating greater severity of depressive symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with treatment-related adverse events after PEARL as assessed by the Swiss Psychedelic Side Effects Inventory (SPSI). | T3 (6 weeks after last follow up) | The SPSI is a 32-item self-report measure designed to systematically assess adverse effects experienced by participants in studies involving psychedelic drugs and MDMA. The inventory contains 32 clinically relevant side effects and assesses severity, impact, duration, treatment-relatedness and timing. |
| Change in mean anxiety symptoms from baseline to T3 as assessed by the Generalized Anxiety Disorder (GAD-7) scale. | T3 (6 weeks after last follow up) | The 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. |
| Change in death-related distress from baseline to T3 as assessed by the Death and Dying Distress Scale (DADDS). | T3 (6 weeks after last follow up) | The 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. |
| Change in demoralization symptoms from baseline to T3 as assessed by the Demoralization Scale (DS). | T3 (6 weeks after last follow up) | The 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. |
| Change in spiritual well-being from baseline to T3 as assessed by the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-Sp). | T3 (6 weeks after last follow up) | The 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. |
| Change in quality of life from baseline to T3 as assessed by the Quality of Life at the End of Life-Cancer Scale (QUAL-EC). | T3 (6 weeks after last follow up) | 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. |
| Number of participants with treatment-related adverse events as assessed by CTCAE v6 and the Monitor Rating Questionnaire (MRQ). | T3 (6 weeks after last follow up) | The MRQ is clinician-rated and administered during the dosing session. It is adapted from the measure used by Griffiths et al. to monitor elevated heart rate and blood pressure, confusion, headache, nausea/vomiting, anxiety, and paranoia. Adverse events will be tracked until study completion. |
| Recruitment feasibility as assessed by the number of participants referred and screened, the number that meet eligibility criteria, and the number of these participants who consent to participate. | T3 (6 weeks after last follow up) | Used to assess the feasibility of a larger PEARL therapy RCT |
| Retention feasibility as assessed by the number of participants completing study measures across all time points. | T3 (6 weeks after last follow up) | Used to assess the feasibility of a larger PEARL therapy RCT |
| Adherence feasibility as assessed by the number of participants completing all PEARL sessions. | T3 (6 weeks after last follow up) | Used to assess the feasibility of a larger PEARL therapy RCT |
Countries
Canada
Contacts
CONTACTSarah Hales, MD
Outcome results
None listed