Epidiolex (CBD) in Patients With Biochemically Recurrent Prostate Cancer

A Phase I/Ib Study on the Safety of Epidiolex in Patients With Prostate Cancer With Rising PSA After Localized Therapy With Either Surgery or Radiation

The purpose of this phase I/Ib study is to determine the safety profile of Epidiolex (CBD oil) in biochemically recurrent prostate cancer patients. The study consists of a dose escalation part and dose expansion part. The dose expansion part of the study will use the maximum tolerated dose (MTD) determined in the dose escalation part to assess the activity, safety and tolerability of the investigational product in patients with biochemically recurrent prostate cancer after localized therapy with either surgery or radiation.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer; Prostate Adenocarcinoma; Prostate Cancer Recurrent
• Intervention / Treatment: Drug: Epidiolex Oral Liquid Product; Drug: Epidiolex Oral Liquid Product

Detailed Description

Cannabinoids (CBD) have been widely used in medicines for centuries to control pain, nausea or vomiting, and to stimulate appetite, especially in cancer patients. Both cannabinoids receptor 1(CB1) and cannabinoids receptor 2 (CB2) were highly expressed in cultured prostate cancer cells compared to normal prostate cell lines. CBD inhibits tumor growth in xenograft model.

Clinicians have been challenged to improve the treatment of biochemically recurrent (BCR) prostate cancer in which prostatic specific antigen (PSA) rises without radiological or clinical progression years after localized treatment (radical prostatectomy or radiation therapy) with or without hormonal treatment. Approximately 50-90% of men with high-risk prostate cancer will experience a BCR. Based on the abovementioned preclinical observations of CBD's effect on prostate cancer and its safety data in two non-cancer populations, a phase I study of CBD in men with biochemically recurrent prostate cancer will be conducted.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Markey Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Completion of localized therapy (prostatectomy or radiotherapy) for prostate adenocarcinoma (either histologically or cytologically confirmed)
• Biochemical (PSA) recurrence, defined as: * PSA of >= 0.2 ng/ml that has increased above nadir following radical prostatectomy OR * PSA increase of 2.0 ng/ml above post-therapy nadir after radiotherapy NOTE: PSA measured at two consecutive time points (separated by 4 or more weeks) is required in order to demonstrate the requisite increase in PSA
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Absolute neutrophil count >= 1,500/microliters (at baseline [pre-study])
• Platelets >= 80,000/microliters (at baseline [pre-study])
• Total bilirubin =< institutional upper limit of normal (at baseline [pre-study])
• Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase) =< institutional upper limit of normal (at baseline [pre-study])
• Glomerular filtration rate (GFR) >= 30 mL/min/1.73 m^2 using the Cockcroft-Gault formula (at baseline [pre-study])
• Patients with a prior or concurrent malignancy (non-prostate) whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen as determined by the treating physician are eligible
• Given that worsening of an underlying state of mental depression or suicidal ideation has been reported with Epidiolex, patients should be carefully screened for depression at baseline and if there are indications or a history of depression it is strongly recommended that these patients be closely followed together with behavioral health or psychiatric medical support. Patients with an established diagnosis of depression that, in the assessment of the investigator may make the administration of Epidiolex hazardous, should not be enrolled on this protocol
• Concurrent use of over-the-counter CBD oil, Marinol or marijuana is not permitted. Patients with a history of current over-the-counter CBD oil, Marinol or marijuana use for any reason are eligible only if they do the following: * Complete a one-week washout period prior to study initiation * Refrain from non-study related CBD oil, Marinol or marijuana use while on-study
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• History of hypersensitivity to Epidiolex (cannabidiol) or sesame seeds (one of the inactive ingredients in Epidiolex)
• Any radiological evidence of metastatic disease (determined by standard of care computed tomography [CT] scans of abdomen. pelvis, chest, whole body bone scan or Axium positron emission tomography scan). Questionable lesions on bone scan will be confirmed by standard of care methods such as plain X-rays or Axium positron emission tomography scan, if not previously performed
• Receipt of prior cytotoxic chemotherapy for recurrent prostate cancer
• Use of androgen deprivation therapy (for example, bicalutamide, flutamide, nilutamide, or leuprolide acetate) concurrently or within the previous 3 months.
• Uncontrolled intercurrent illness such as active infections. Other illnesses will be evaluated and eligibility status determined at the discretion of the treating physician and the investigator
• Psychiatric illness/social situations that would limit compliance with study requirements
• Concomitant use of valproate or clobazam
• Concurrent use of over-the-counter CBD oil, Marinol or marijuana
• Epidiolex is a moderate inhibitor of CYP2C19 and a moderate/strong inhibitor of CYP3A4, therefore concurrent use of CYP2C19 substrates is not allowed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation: Epidiolex 600 mg; Cohort 1 participants with rising PSA after failure of localized therapy will receive 600 mg oral solution Epidiolex once daily for a total of 90 days in the absence of disease progression or unacceptable toxicity followed by a 10-day taper with 30 days of follow up after the discontinuation (last dose) of Epidiolex	Drug: Epidiolex Oral Liquid Product; 600 mg Oral solution; Other Names: CBD oil; Drug: Epidiolex Oral Liquid Product; 800 mg oral solution; Other Names: CBD oil
Experimental: Dose Escalation: Epidiolex 800 mg; Cohort 2 participants with rising PSA after failure of localized therapy will receive 800 mg oral solution Epidiolex once daily for a total of 90 days in the absence of disease progression or unacceptable toxicity followed by a 10-day taper with 30 days of follow up after the discontinuation (last dose) of Epidiolex	Drug: Epidiolex Oral Liquid Product; 600 mg Oral solution; Other Names: CBD oil; Drug: Epidiolex Oral Liquid Product; 800 mg oral solution; Other Names: CBD oil
Experimental: Dose Expansion: Epidiolex 800 mg; Expansion Cohort participants with rising PSA after failure of localized therapy will receive the MTD of 800 mg oral solution Epidiolex once daily for a total of 90 days in the absence of disease progression or unacceptable toxicity followed by a 10-day taper with 30 days of follow up after the discontinuation (last dose) of Epidiolexdose	Drug: Epidiolex Oral Liquid Product; 600 mg Oral solution; Other Names: CBD oil; Drug: Epidiolex Oral Liquid Product; 800 mg oral solution; Other Names: CBD oil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Dose-limiting Toxicities (Treatment-related Adverse Events) as Assessed by the CTCAE v5.0	DLT was defined as grade ≥3 nausea, vomiting, diarrhea that persists >72 h despite optimal anti-emetics and anti-diarrhea treatment, grade ≥3 hematological adverse events (AEs), or grade ≥2 suicidal ideation.Treatment-related adverse events are those that comprise a dose-limiting toxicity within 30 days after initiation of Epidiolex (i.e., acute DLT). Additionally, Treatment-related adverse events will continue to be monitored for a total of 90 days.	up to 90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants With Biochemical Response.	Biochemical response (25% change from baseline) will be determined by the measurement of PSA at baseline and approximately every 4 weeks during treatment.	within 90 days
Change in PSA Velocity From Baseline Throughout the Treatment Period as an Indication of Biochemical Response.	Biochemical response will be determined by measurement of PSA approximately every 4 weeks during treatment. PSA velocity is the calculation (PSA final measurement - PSA initial measurement) / number of years between measurements.	within 90 days
Change in Testosterone Levels From Baseline Throughout the Treatment Period as an Indication of Biochemical Response	Biochemical response will be determined by measurement of total testosterone level approximately every 4 weeks during treatment.	Baseline, Day 1 of Cycle 1 (each cycle is 4 weeks), Day 1 of Cycle 2, Day 1 of Cycle 3, and 1 month post treatment (up to 16 weeks)
Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30)	The EORTC quality of life questionnaire (QLQ) 30 is a validated 30-item patient-reported questionnaire assessing quality of life among cancer populations. The quality of life questionnaire-C30 is the core QOL instrument, with 30 items that comprise five functioning scales (physical, social, role, cognitive, and emotional functioning), eight symptom scales (fatigue, nausea/vomiting, pain, dyspnea, sleep disturbances, appetite loss, constipation, and diarrhea), financial impact, and overall quality of life. All raw item scores are transformed to scale scores, linearly converted to range from 0 to 100. For the functioning scales and global QOL, higher scores indicate better functioning. For the symptom scales, higher scores indicate higher symptom burden.	Baseline
Health-related Quality of Life (EORTC Quality of Life Questionnaire-C30)	The EORTC quality of life questionnaire (QLQ) 30 is a validated 30-item patient-reported questionnaire assessing quality of life among cancer populations. The quality of life questionnaire-C30 is the core QOL instrument, with 30 items that comprise five functioning scales (physical, social, role, cognitive, and emotional functioning), eight symptom scales (fatigue, nausea/vomiting, pain, dyspnea, sleep disturbances, appetite loss, constipation, and diarrhea), financial impact, and overall quality of life. All raw item scores are transformed to scale scores, linearly converted to range from 0 to 100. For the functioning scales and global QOL, higher scores indicate better functioning. For the symptom scales, higher scores indicate higher symptom burden.	12 weeks
Prostate Cancer-Specific Quality of Life (EORTC Quality of Life Questionnaire-PR25)	The EORTC quality of life questionnaire (QLQ)-PR25 is a validated 25-item patient-reported questionnaire which complements the EORTC QLQ-C30,core QOL questionnaire. The QLQ-PR25 comprises 25 items assessing sequelae specific to prostate cancer and its treatment, and thus, is intended to supplement the EORTC QLQ-C30. The 25 items comprise six prostate-specific scales: Urinary, Bowel, Use of Incontinence Aids, Prostate Cancer Treatment-Related Symptoms, Sexual Active and Sexual Function. Raw item scores are linearly transformed to a 0 to 100 scale (i.e., same unit of measurement used by the core QLQ-C30 questionnaire). For the QLQ-PR25, higher scores on symptom domains (e.g., urinary, bowel, etc.) indicate greater symptom burden. Higher scores on function domains (e.g., Sexual Function) indicate better functioning.	Baseline
Prostate Cancer-Specific Quality of Life (EORTC Quality of Life Questionnaire-PR25)	The EORTC quality of life questionnaire (QLQ)-PR25 is a validated 25-item patient-reported questionnaire which complements the EORTC QLQ-C30,core QOL questionnaire. The QLQ-PR25 comprises 25 items assessing sequelae specific to prostate cancer and its treatment, and thus, is intended to supplement the EORTC QLQ-C30. The 25 items comprise six prostate-specific scales: Urinary, Bowel, Use of Incontinence Aids, Prostate Cancer Treatment-Related Symptoms, Sexual Active and Sexual Function. Raw item scores are linearly transformed to a 0 to 100 scale (i.e., same unit of measurement used by the core QLQ-C30 questionnaire). For the QLQ-PR25, higher scores on symptom domains (e.g., urinary, bowel, etc.) indicate greater symptom burden. Higher scores on function domains (e.g., Sexual Function) indicate better functioning.	12 weeks

Collaborators and Investigators

• Sponsor: Zin W Myint
• Investigators: Principal Investigator: Zin W. Myint, MD, University of Kentucky

Study record dates

Study Major Dates

• Study Start (Actual): August 3, 2020
• Primary Completion (Actual): August 20, 2021
• Study Completion (Actual): August 20, 2021

Study Registration Dates

• First Submitted: June 6, 2020
• First Submitted That Met QC Criteria: June 9, 2020
• First Posted (Actual): June 11, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 11, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Prostate; Rising PSA; Epidiolex; CBD Oil
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Anticonvulsants; Cannabidiol
• Other Study ID Numbers: MCC-20-GU-74-PMC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No