Psilocybin With Psychotherapy for Improving Chronic Pain in Cancer Patients Requiring Opioids

NCT06827054 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: I-3914823NCI-2024-10761
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies whether psilocybin with psychotherapy is safe and if it works for improving chronic pain in cancer patients who require opioids to manage their pain. Psilocybin is taken from the mushroom Psilocybe mexicana. Psilocybin acts on the brain to cause hallucinations (sights, sounds, smells, tastes, or touches that a person believes to be real but are not real). This may impact a patient's "total pain", a view that accounts for the psychological, spiritual, and social factors that contribute to their experience of pain. Psychotherapy uses methods such as discussion, listening, and counseling to help patients change the way they react to environmental triggers that may cause a negative reaction. Giving psilocybin with psychotherapy may be safe and helpful for improving chronic pain in cancer patients who require opioids to manage their pain.

Conditions

Hematopoietic and Lymphatic System Neoplasm; Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (7)

• Incidence of adverse events (AEs)

  AE assessments will be performed at each treatment session and all subsequent in-person and virtual visits. This will be clinician-observed events. These evaluations will utilize the established Common Terminology Criteria for Adverse Events version 5.0. AEs will be summarized by attribution and grade using frequencies and relative frequencies, where the grade 3+ AE rate will be estimated with 90% credible regions obtained by Jeffrey's prior method. Additionally, a continual safety monitoring plan will be utilized to ensure study suspension should the AE rates exceed pre-defined thresholds.

  From start date of intervention to 30 days after the last intervention

• Change in Vital signs

  Continuous Vital signs will be assessed and summarized by timepoint using the appropriate descriptive statistics. The change in these measures will be modeled as a function of time and a random subject effect using linear mixed models, where tests about the appropriate contrasts of model estimates will be used to identify significant changes relative to pre-treatment levels. All model assumptions will be verified graphically.

  Up to baseline, dosing sessions 1 and 2 up to day 84

• Incidence of clinically important changes in ICG parameters

  To assess any changes in EKG records from baseline EKG to day 28 EKG

  At baseline and day 28

• Change in risk for suicide

  Will be assessed using the Columbia-Suicide Severity Rating Scale. Will be summarized by timepoint using the appropriate descriptive statistics. The change will be modeled as a function of time and a random subject effect using linear mixed models, where tests about the appropriate contrasts of model estimates will be used to identify significant changes relative to pre-treatment levels. All model assumptions will be verified graphically.

  At baseline, dosing sessions 1, 2, 3, 5, and 7, and days 28, 56, and 84

• Change in cognitive function

  A Montreal Cognitive Assessment will be provided prior to the first dosing session, at two-hour intervals during the first two dosing sessions and subsequent dosing sessions if a dose reduction occurred, and once during subsequent visits.

  At dosing sessions 1-3 and days 28, 56, and 84

• Recruitment rate

  Recruitment will be measured as a percentage of participants who were contacted for prescreening that were enrolled. Will be estimated with 90% credible regions obtained by Jeffrey's prior method.

  Up to day 84

• Retention rate

  Retention rate will be measured as a percentage of participants who enrolled that completed the trial, determined by completion of visit 19. Will be estimated with 90% credible regions obtained by Jeffrey's prior method.

  Up to day 84

Secondary Outcomes (2)

• Change in average pain intensity

  At baseline and days 3, 7, 28, 56, and 84

• Change in rescue opioid requirement

  At baseline and days 3, 7, 28, 56, and 84

Study Arms (1)

Supportive care (psychotherapy, psilocybin)

EXPERIMENTAL

Patients attend two preparatory psychotherapy sessions. Patients then receive psilocybin PO BIW for 4 weeks (8 doses total) in the absence of unacceptable toxicity and attend three integration psychotherapy sessions over 1.5 hours each during psilocybin dosing sessions 2, 4, and 6. Patients may optionally attend additional psychotherapy sessions as needed during follow-up. Additionally, patients undergo fMRI and collection of blood and urine samples throughout the study.

Procedure: Biospecimen Collection; Procedure: Functional Magnetic Resonance Imaging; Other: Interview; Drug: Psilocybine; Behavioral: Psychotherapy; Other: Questionnaire Administration

Interventions

Biospecimen Collection PROCEDURE

Undergo collection of blood and urine samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Supportive care (psychotherapy, psilocybin)

Functional Magnetic Resonance Imaging PROCEDURE

Undergo fMRI

Also known as: fMRI, Functional MRI

Supportive care (psychotherapy, psilocybin)

Interview OTHER

Ancillary studies

Supportive care (psychotherapy, psilocybin)

Psilocybine DRUG

Given PO

Also known as: CY-39, Indocybin, Psilocybin

Supportive care (psychotherapy, psilocybin)

Psychotherapy BEHAVIORAL

Attend psychotherapy sessions

Also known as: talk therapy

Supportive care (psychotherapy, psilocybin)

Questionnaire Administration OTHER

Ancillary studies

Supportive care (psychotherapy, psilocybin)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 and ≤ 75 years old
• Diagnosis of active cancer, any stage
• Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Estimated prognosis of ≥ 3 months at the time of enrollment, determined by participant's primary oncologist or palliative physician
• Diagnosis of moderate to severe pain (reported average pain score ≥ 4 on the 11-point Numerical Rating Scale) that is chronic (≥ 3 months) and secondary to cancer or cancer treatment
• Pain regimen has been escalated to opioid therapy
• Participants must be on stable pain regimen for at least one month prior, with no intention to adjust pain regimen during the study period
• Participants must be ≥ 4 weeks beyond treatments/procedures that, in the opinion of the study physician, would significantly affect outcomes related to pain and physical function (e.g., surgery or radiation). Participants may otherwise receive cancer-directed treatment throughout the study period
• Have no known procedures/treatments scheduled in advance that would prohibit patient from completing or significantly delaying completion of the study
• The participant has no vacations or plans to be out of town during their study enrollment
• Participants must not plan for additional treatments/procedures that, in the opinion of the study physician, would significantly affect outcomes related to pain and physical function (e.g., surgery or radiation) for ≥ 4 weeks following psilocybin treatment initiation. Participants may otherwise receive cancer-directed treatment throughout the study period
• No use of other illicit substances (excluding cannabis) within the past year based on self-report at screening and routine urine toxicology screen
• Participants must be able to read, write, and speak English
• Participants must be able to swallow pills
• Agree to refrain from using any unprescribed psychoactive drugs, including alcoholic beverages, ≤ 24 hours of before each psilocybin administration. Exceptions include:

You may not qualify if:

• Participants who are pregnant or breast-feeding
• Participants of childbearing potential who decline to use a highly effective dual contraceptive method for the duration of the study
• Participants with a condition impairing oral intake or digestive absorption
• Cognitive impairment as defined by Montreal Cognitive Assessment (MOCA) score \< 23
• Medical conditions or serious abnormalities of complete blood count, chemistries, or electrocardiography (ECG) that in the opinion of the study physician would preclude safe participation in the trial. Some examples include: congestive heart failure, valvular heart disease, recent acute myocardial infarction or evidence of ischemia, clinically significant arrhythmias (e.g., ventricular fibrillation, torsades) or clinically significant ECG abnormality (e.g. corrected QT interval using Fridericia's Correction Formula \[QTcF\] interval \> 450 in males and \> 470 in females), uncontrolled hypertension (systolic blood pressure \[BP\] ≥ 140 or diastolic BP ≥ 90 on three separate occasions), congenital long QT syndrome, renal dysfunction (i.e. creatinine clearance \[CrCl\] \< 40 mL/min), liver cirrhosis or hepatic dysfunction (indicated by gamma-glutamyltransferase \[GGT\], aspartate aminotransferase \[AST\], or alanine aminotransferase \[ALT\] \> 3 x ULN \[upper limit of norm\] or total bilirubin \[bili\] \> 3.0 mg/dl, or Child Pugh over class C), paraneoplastic syndrome, respiratory failure, dementia, delirium, known cerebral aneurysm, seizure disorder, stroke/transient ischemic attack (TIA) in past year, cancer with known central nervous system (CNS) involvement, previously treated brain metastasis, or other major CNS disease
• Participants who have a personal history of, or a current diagnosis of the following: primary psychotic disorder, major depressive disorder with psychotic features, bipolar affective disorder type 1 or history of or current dissociative identity disorder
• Participants who have an ongoing substance use disorder (defined as active in the past year)
• Participants with first-degree relatives with schizophrenia or bipolar disorder may be eligible depending on their age and personal and family psychiatric history. The decision will be made by the principal investigator and study psychiatrist or on-call psychiatric provider based on risk assessment
• Active suicidal behavior (interrupted or aborted attempt; preparatory acts) as assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) connotating either passive or active suicidal intent; OR one of the following:
• History of suicide attempt(s) within the past year (≤ 365 days)
• Have any suicidal ideation or thoughts, in the opinion of the study physician or principal investigator (PI), that presents a serious risk of suicidal or self-injurious behavior
• Any contraindications to undergoing an fMRI scan, including having metal implants or metal fragments in the body
• Participants who have hypersensitivity to the ingredients of the IMP (Investigational Medicinal Product) listed below:
• Indol alkaloids including psilocybin and psilocin
• Constituents of Psilocybe cubensis including protein, fats, carbohydrates, ergosterols, beta-glucan, and polyphenols

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Interventions

Specimen Handling; Interviews as Topic; Psilocybin; Psychotherapy

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Data Collection; Epidemiologic Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines; Behavioral Disciplines and Activities

Study Officials

• William Alexander

  Roswell Park Cancer Institute

  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 22, 2025
• First Posted: February 14, 2025
• Study Start (Estimated): May 15, 2026
• Primary Completion (Estimated): May 5, 2027
• Study Completion (Estimated): May 5, 2027
• Last Updated: March 24, 2026

Record last verified: 2026-03

Locations

US (1)