Trial Title:
Psilocybin-Assisted Psychotherapy in Patients With Advanced Cancer on Maintenance Therapy
NCT ID:
NCT06200155
Condition:
Depression, Anxiety
Psilocybin-Assisted Psychotherapy
Advanced Cancer
Conditions: Official terms:
Neoplasms
Depression
Niacin
Psilocybin
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Supportive Care
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Intervention:
Intervention type:
Drug
Intervention name:
Psilocybin
Description:
Given by PO
Arm group label:
Arm A
Intervention type:
Other
Intervention name:
Niacin
Description:
Given by PO
Arm group label:
Arm B
Summary:
To learn about the feasibility, safety, and effects of psilocybin-assisted psychotherapy
on depression and/or anxiety in participants who are being treated for advanced cancer.
Detailed description:
Primary Objective
To examine the feasibility, safety, effect size estimates of psilocybin-assisted
psychotherapy for participants with depression and/or anxiety who are being actively
treated for advanced cancer. Feasibility will be measured as: At least 20% of eligible
participants consent and at least 60% of consented participants complete the two doses of
treatment.
Secondary Objectives
1. Determine whether psilocybin-assisted psychotherapy improves measures of quality of
life (e.g., sleep, pain, functional status) and psychosocial well-being (e.g.,
finding meaning and post-traumatic growth), as measured by the following: PHQ-9,
GAD-7, PROMIS-10, PROMIS-A, PROMIS-D, MEQ30 (mystical experience), Flourishing
scale, mDES, 5D-ASC (altered states), and Posttraumatic Growth Inventory.
2. Determine whether psilocybin-assisted psychotherapy improves functional status per
clinician-rated outcome measures.
3. Assess the effects of psilocybin-assisted psychotherapy on cancer treatment
adherence determined by the likelihood that participants will follow the prescribed
treatment (adherence) and continue the treatment for the duration prescribed
(persistence) for these maintenance therapies.
4. Measure the change in inflammatory markers (IL6, TNF, and CRP) and in frequency and
activation status of peripheral immune cell populations assessed by immune
monitoring through flow cytometry.
5. Examine changes in central nervous system plasticity through the use of fMRI,
specifically changes in 5-HT2A-rich and higher-order functional networks, as well as
a global increase in brain network integration.
6. Evaluate the Impact on MDASI measurements.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Participants must have one of the following histology documented tumor types:
non-small cell lung carcinoma, renal cell carcinoma, urothelial carcinoma, prostate
cancer, head and neck squamous cell carcinoma, ovarian cancer, breast cancer,
gastric/GEJ cancer, cervical, anal, or MSI-high
2. Documentation of locally advanced, recurrent, or metastatic incurable malignancy
that has partially responded or progressed after at least 1 available standard
therapy and disease is stable (no progression of disease for 3 months or more on
current treatment regimen)
3. No prior grade 3 AEs on current standard of care cancer treatment regimen;
4. Age ≥ 25 years; as by the age of 25 brain is fully developed.
5. Have a DSM-V psychiatric diagnosis, as determined by the SCID (Structured Clinical
Interview for DSM, by a board certified psychiatrist), of one or more of the
following Axis I psychiatric disorders that is judged to have been precipitated by
the psychological stress of the cancer diagnosis: Generalized Anxiety Disorder;
Acute Stress Disorder; Posttraumatic Stress Disorder; Major Depressive Disorder;
Dysthymic Disorder; Adjustment Disorder with Anxiety; Adjustment Disorder with
Depressed Mood; Adjustment Disorder with Mixed Anxiety and Depressed Mood;
Adjustment Disorder with Disturbance of Conduct; Adjustment Disorder with
Disturbance of Emotions and Conduct. Psychiatric diagnosis are determined by a MD
Anderson board certified psychiatrist.
6. At least 6 months life expectancy as per primary medical oncologist.
7. Have an ECOG performance status of 0, 1, or 2.
8. Must have no major cognitive impairment and be oriented to person, place, and time
(e.g. mini mental exam).
9. Must demonstrate willingness to travel to MD Anderson Cancer center for all
treatment and follow-up sessions, as well as consent to complete all evaluation
instruments and assessments.
10. Agree to abstain from any nicotine products for at least 12 hours prior to
psilocybin administration until approximately 12 hours after (or when all
post-session questionnaires have been completed) as well as on days of salivary
sample collection.
11. Refrain from any psychoactive drugs (including alcohol) for 48 hours prior to
psilocybin sessions (except as described above for nicotine and caffeine) and must
refrain from psychoactive drugs 12 hours after psilocybin sessions. Must consent to
urine drug screen (UDS) which will be given before receiving psilocybin.
Participants with positive drug test will be retested (UDS) after 6 weeks and
included if the repeated UDS is negative. Participant tested positive for a
prescribed substance are eligible. Participant failing on the 2nd test (UDS) will be
excluded.
12. Must be free from any regularly scheduled psychotropic (antidepressant/anxiolytic
class) medications and those with primary MOA on serotonergic neurons (e.g.,
ondansetron) for a minimum of 2 weeks prior to study or 4 weeks for SSRI.
Intermittent or PRN use of short-acting anxiolytics may be permitted as defined
below in exclusionary criteria).
13. Inhibitors of monoamine oxidase, UGT1A9, 1A10, and aldehyde or alcohol dehydrogenase
should be discontinued 5 half-lives prior to active dose of psilocybin.
14. Eligible participants will have a responsible individual that will provide
transportation home after the psilocybin session is complete.
15. Fluent in English
Exclusion Criteria:
1. History of depression prior to cancer diagnosis.
2. Clinically significant suicidality or high risk of completed suicide defined as:
i. Answer 'Yes' to C-SSRS Suicidal Ideation items 4 or 5 within the last 2 months at
Screening or 'since last visit' at Baseline ii. Report having had any C-SSRS
Suicidal Behavior item within the past 12 months at Screening or 'since last visit'
at Baseline, as defined by 'Yes' to any of the following on the C-SSRS: actual
attempt, interrupted attempt, aborted attempt, or preparatory acts iii. Have any
suicidal ideation or thoughts, in the opinion of the study physician or PI, that
presents a serious risk of suicidal or self-injurious behavior
3. History of bipolar disorder, psychosis (of any nature), and seizures.
4. Functionally limiting comorbid conditions such as second primary malignancies in CNS
or chest, and history of total laryngectomy or total .glossectomy.
5. ECG with QTc > 450.
6. Patients with metal implants.
7. Asymptomatic ALT or AST elevations >/= 5X upper limit of normal, symptomatic ALT or
AST elevations >/= 2X upper limit of normal, or total bilirubin >/= 2X upper limit
of normal.
8. The effects of psilocybin on the developing human fetus are unknown. For this
reason, pregnant women will be excluded (Urine test for screening), women of
child-bearing potential and men must agree to use adequate contraception (hormonal
or barrier method of birth control; abstinence) prior to study entry and for the
duration of study participation. This includes all female participants, between the
onset of menses (as early as 8 years of age) and 55 years unless the participant
presents with an applicable exclusionary factor which may be one of the following:
Postmenopausal (no menses in greater than or equal to 12 consecutive months).
History of hysterectomy or bilateral salpingo-oophorectomy. Ovarian failure
(Follicle Stimulating Hormone and Estradiol in menopausal range, who have received
Whole Pelvic Radiation Therapy).
History of bilateral tubal ligation or another surgical sterilization procedure.
Approved methods of birth control are as follows: Hormonal contraception (i.e. birth
control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine
device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy,
Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging
in sexual activity for the total duration of the trial and the drug washout period
is an acceptable practice; however periodic abstinence, the rhythm method, and the
withdrawal method are not acceptable methods of birth control. Should a woman become
pregnant or suspect she is pregnant while she or her partner is participating in
this study, she should inform her treating physician immediately.
9. persons with first- or second-degree relatives who have schizophrenia or other
psychotic disorders, or bipolar I or II disorder.
10. Actively progressing disease as defined by the primary oncologist.
11. Vulnerable populations, including children and cognitively impaired patients, will
not be enrolled in this study.
12. Participants with brain metastases.
13. Risk for hypertensive crisis defined as Screening, Baseline, and Medication Session
(prior to dosing) Blood Pressure >140/90 mmHg and HR> 90 bpm.
14. Unstable medical conditions or serious abnormalities of complete blood count,
chemistries, or ECG that in the opinion of the study physician would preclude safe
participation in the trial. Some examples include:
i. Uncompensated congestive heart failure ii. Clinically significant arrhythmias
(e.g., ventricular fibrillation, torsades) or clinically significant ECG abnormality
(i.e., QTC interval > 450) iii. Recent acute myocardial infarction or evidence of
ischemia iv. Malignant hypertension v. Congenital long QT syndrome vi. Acute renal
failure vii. Severe hepatic impairment viii. Respiratory failure
15. Significant central nervous system (CNS) pathology. Some examples include:
i. Primary or secondary cerebral neoplasm ii. Epilepsy iii. History of stroke iv.
Cerebral aneurysm v. Dementia vi. Delirium
16. a. High risk of adverse emotional or behavioral reaction based on investigator's
clinical evaluation. Examples include: i. Agitation ii. Violent behavior b. Active
substance use disorders (SUDs) defined as: DSM-5 criteria for moderate or severe
alcohol or drug use disorder (excluding caffeine and nicotine) within the past year
c. Extensive use of serotonergic hallucinogens (e.g., LSD, psilocybin) defined as:
i. Any use in the last 12 months ii. >25 lifetime uses d. History of hallucinogen
persisting perception disorder (HPPD) e. Concurrent Medications i. Antidepressants
ii. Centrally-acting serotonergic agents (e.g., MAO inhibitors) iii. Antipsychotics
(e.g., first and second generation) iv. Mood stabilizers (e.g., lithium, valproic
acid) v. Aldehyde dehydrogenase inhibitors (e.g., disulfiram) vi. Significant
inhibitors of UGT 1A0 or UGT 1A10 vii. Niacin. Note: If taking any supplement
containing niacin, agrees to suspend use for at least five days prior to dosing and
for the duration of the study f. Have a positive urine drug test including
Amphetamines, Barbiturates, Buprenorphine, Benzodiazepines, Cocaine, Cannabis,
Methamphetamine, MDMA, Methadone, Opiates (Morphine, Oxycodone), Phencyclidine
(PCP), and Tetrahydrocannabinol (THC).
i. Note: Prescribed opiate medications (e.g., cancer-related pain) will be allowed
to continue through the study period for participants who have been on a stable dose
of such medicine for at least 1 month prior to Screening, as determined during
review of concomitant medications.
ii. Note: Prescribed benzodiazepine medications and nonbenzodiazepine sleeping
medications will be allowed to continue through the study period for participants
who have been on a stable dose of such a medicine for at least 6 weeks prior to
Screening, as determined during review of concomitant medications.
iii. Note: Participants using cannabis, including legal cannabis, for any purposes
must agree to refrain from use beginning at Screening, as confirmed with a negative
Baseline drug test, and through to the end of the study.
iv. Note: Participants using prescribed psychostimulants (amphetamines and Ritalin),
must agree to refrain from use two weeks prior to baseline visit, as confirmed with
a negative Baseline drug test, and through to the end of the study.
g. Have a psychiatric condition judged to be incompatible with establishment of
rapport with the study therapists or safe exposure to psilocybin h. Have any
psychological or physical symptom, medication or other relevant finding prior to
randomization, based on the clinical judgment of the PI or relevant clinical study
staff that would make a participant unsuitable for the study.
i. Have an allergy or intolerance to any of the materials contained in either drug
product j. Be enrolled in another clinical trial assessing intervention(s) for
anxiety, depression, and/or existential distress (e.g., pharmacologic or
psychotherapeutic interventions)
17. Participants who have any of the below niacin contraindications:
1. Active liver disease or unexplained persistent elevations in hepatic
transaminases
2. active peptic ulcer disease
3. arterial bleeding
4. Hypersensitivity to niacin or any component of this medication
18. BP> 200/110 (or malignant hypertension defined as 200/120) would prevent a patient
from receiving psilocybin dosing and would prompt calling a physician during blood
pressure monitoring for cardiac risk evaluation.
Gender:
All
Minimum age:
25 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Moran Amit, MD
Phone:
713-794-5304
Email:
mamit@mdanderson.org
Investigator:
Last name:
Moran Amit, MD
Email:
Principal Investigator
Start date:
April 16, 2024
Completion date:
December 31, 2026
Lead sponsor:
Agency:
M.D. Anderson Cancer Center
Agency class:
Other
Collaborator:
Agency:
Gateway for Cancer Research
Agency class:
Other
Source:
M.D. Anderson Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06200155
http://www.mdanderson.org
