Clinical Trials /

Epidiolex (CBD) in Patients With Biochemically Recurrent Prostate Cancer

NCT04428203

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Epidiolex (CBD) in Patients With Biochemically Recurrent Prostate Cancer
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: MCC-20-GU-74-PMC
  • NCT ID: NCT04428203

Conditions

  • Prostate Cancer Recurrent
  • Prostate Cancer
  • Prostate Adenocarcinoma

Interventions

DrugSynonymsArms
Epidiolex Oral Liquid ProductCBD oilsingle arm

Purpose

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

      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.
    

Trial Arms

NameTypeDescriptionInterventions
single armExperimentalA Phase I/Ib on the Safety of Epidiolex in Patients with Prostate Cancer with Rising PSA after Localized Therapy with either Surgery or Radiation
  • Epidiolex Oral Liquid Product

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with dose-limiting toxicities (treatment-related adverse events) as assessed by the CTCAE v5.0
Time Frame:up to 90 days
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Change in serial PSA levels from baseline throughout the treatment period as an indication of biochemical response.
Time Frame:within 90 days
Safety Issue:
Description:Biochemical response will be determined by the measurement of PSA at baseline and approximately every 4 weeks during treatment.
Measure:Change in PSA velocity from baseline throughout the treatment period as an indication of biochemical response.
Time Frame:within 90 days
Safety Issue:
Description: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.
Measure:Change in testosterone levels from baseline throughout the treatment period as an indication of biochemical response
Time Frame:up to 90 days
Safety Issue:
Description:Biochemical response will be determined by measurement of testosterone level approximately every 4 weeks during treatment.
Measure:Health-related quality of life (EORTC quality of life questionnaire-C30)
Time Frame:up to 90 days
Safety Issue:
Description: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.
Measure:Prostate Cancer-Specific Quality of Life (EORTC quality of life questionnaire-PR25)
Time Frame:up to 90 days
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Zin W Myint

Trial Keywords

  • Prostate
  • Rising PSA
  • CBD Oil
  • Epidiolex

Last Updated

August 3, 2020