Epidiolex (CBD) in Patients With Biochemically Recurrent Prostate Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Prostate Cancer Recurrent, Prostate Cancer, Prostate Adenocarcinoma

Intervention / Treatment
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* Drug: Epidiolex Oral Liquid Product


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: single arm<br>A Phase I/Ib on the Safety of Epidiolex in Patients with Prostate Cancer with Rising PSA after Localized Therapy with either Surgery or Radiation | Drug: Epidiolex Oral Liquid Product<br>* patients with rising PSA after failure of localized therapy will receive Epidiolex PO once daily for up to 12 weeks in the absence of disease progression or unacceptable toxicity. Patients receive an Epidiolex taper for 7-10 days after withdrawing from study for any reason or completion of the study period.<br>* Other names: CBD oil;|

What is the study measuring?
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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 | 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 |
| --- | --- | --- |
| Change in serial PSA levels from baseline throughout the treatment period as an indication of biochemical response. | Biochemical response 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 change in PSA levels over time. | 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 testosterone level approximately every 4 weeks during treatment. | up to 90 days | 
| 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. | up to 90 days | 
| 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. | up to 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epidiolex, Rising PSA, CBD Oil, Prostate