<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04428203</url>
  </required_header>
  <id_info>
    <org_study_id>MCC-20-GU-74-PMC</org_study_id>
    <nct_id>NCT04428203</nct_id>
  </id_info>
  <brief_title>Epidiolex (CBD) in Patients With Biochemically Recurrent Prostate Cancer</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Zin W Myint</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Kentucky</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this phase I/Ib study is to determine the safety profile of Epidiolex (CBD&#xD;
      oil) in biochemically recurrent prostate cancer patients. The study consists of a dose&#xD;
      escalation part and dose expansion part. The dose expansion part of the study will use the&#xD;
      maximum tolerated dose (MTD) determined in the dose escalation part to assess the activity,&#xD;
      safety and tolerability of the investigational product in patients with biochemically&#xD;
      recurrent prostate cancer after localized therapy with either surgery or radiation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cannabinoids (CBD) have been widely used in medicines for centuries to control pain, nausea&#xD;
      or vomiting, and to stimulate appetite, especially in cancer patients. Both cannabinoids&#xD;
      receptor 1(CB1) and cannabinoids receptor 2 (CB2) were highly expressed in cultured prostate&#xD;
      cancer cells compared to normal prostate cell lines. CBD inhibits tumor growth in xenograft&#xD;
      model.&#xD;
&#xD;
      Clinicians have been challenged to improve the treatment of biochemically recurrent (BCR)&#xD;
      prostate cancer in which prostatic specific antigen (PSA) rises without radiological or&#xD;
      clinical progression years after localized treatment (radical prostatectomy or radiation&#xD;
      therapy) with or without hormonal treatment. Approximately 50-90% of men with high-risk&#xD;
      prostate cancer will experience a BCR. Based on the abovementioned preclinical observations&#xD;
      of CBD's effect on prostate cancer and its safety data in two non-cancer populations, a phase&#xD;
      I study of CBD in men with biochemically recurrent prostate cancer will be conducted.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 3, 2020</start_date>
  <completion_date type="Actual">August 20, 2021</completion_date>
  <primary_completion_date type="Actual">August 20, 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with dose-limiting toxicities (treatment-related adverse events) as assessed by the CTCAE v5.0</measure>
    <time_frame>up to 90 days</time_frame>
    <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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in serial PSA levels from baseline throughout the treatment period as an indication of biochemical response.</measure>
    <time_frame>within 90 days</time_frame>
    <description>Biochemical response will be determined by the measurement of PSA at baseline and approximately every 4 weeks during treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in PSA velocity from baseline throughout the treatment period as an indication of biochemical response.</measure>
    <time_frame>within 90 days</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in testosterone levels from baseline throughout the treatment period as an indication of biochemical response</measure>
    <time_frame>up to 90 days</time_frame>
    <description>Biochemical response will be determined by measurement of testosterone level approximately every 4 weeks during treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-related quality of life (EORTC quality of life questionnaire-C30)</measure>
    <time_frame>up to 90 days</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prostate Cancer-Specific Quality of Life (EORTC quality of life questionnaire-PR25)</measure>
    <time_frame>up to 90 days</time_frame>
    <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.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Prostate Cancer Recurrent</condition>
  <condition>Prostate Cancer</condition>
  <condition>Prostate Adenocarcinoma</condition>
  <arm_group>
    <arm_group_label>single arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Epidiolex Oral Liquid Product</intervention_name>
    <description>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.</description>
    <arm_group_label>single arm</arm_group_label>
    <other_name>CBD oil</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Completion of localized therapy (prostatectomy or radiotherapy) for prostate&#xD;
             adenocarcinoma (either histologically or cytologically confirmed)&#xD;
&#xD;
          -  Biochemical (PSA) recurrence, defined as: * PSA of &gt;= 0.2 ng/ml that has increased&#xD;
             above nadir following radical prostatectomy OR * PSA increase of 2.0 ng/ml above&#xD;
             post-therapy nadir after radiotherapy NOTE: PSA measured at two consecutive time&#xD;
             points (separated by 4 or more weeks) is required in order to demonstrate the&#xD;
             requisite increase in PSA&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status =&lt; 2&#xD;
&#xD;
          -  Absolute neutrophil count &gt;= 1,500/microliters (at baseline [pre-study])&#xD;
&#xD;
          -  Platelets &gt;= 80,000/microliters (at baseline [pre-study])&#xD;
&#xD;
          -  Total bilirubin =&lt; institutional upper limit of normal (at baseline [pre-study])&#xD;
&#xD;
          -  Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase/alanine&#xD;
             aminotransferase (ALT)(serum glutamate pyruvate transaminase) =&lt; institutional upper&#xD;
             limit of normal (at baseline [pre-study])&#xD;
&#xD;
          -  Glomerular filtration rate (GFR) &gt;= 30 mL/min/1.73 m^2 using the Cockcroft-Gault&#xD;
             formula (at baseline [pre-study])&#xD;
&#xD;
          -  Patients with a prior or concurrent malignancy (non-prostate) whose natural history or&#xD;
             treatment does not have the potential to interfere with the safety or efficacy&#xD;
             assessment of the investigational regimen as determined by the treating physician are&#xD;
             eligible&#xD;
&#xD;
          -  Given that worsening of an underlying state of mental depression or suicidal ideation&#xD;
             has been reported with Epidiolex, patients should be carefully screened for depression&#xD;
             at baseline and if there are indications or a history of depression it is strongly&#xD;
             recommended that these patients be closely followed together with behavioral health or&#xD;
             psychiatric medical support. Patients with an established diagnosis of depression&#xD;
             that, in the assessment of the investigator may make the administration of Epidiolex&#xD;
             hazardous, should not be enrolled on this protocol&#xD;
&#xD;
          -  Concurrent use of over-the-counter CBD oil, Marinol or marijuana is not permitted.&#xD;
             Patients with a history of current over-the-counter CBD oil, Marinol or marijuana use&#xD;
             for any reason are eligible only if they do the following: * Complete a one-week&#xD;
             washout period prior to study initiation * Refrain from non-study related CBD oil,&#xD;
             Marinol or marijuana use while on-study&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of hypersensitivity to Epidiolex (cannabidiol) or sesame seeds (one of the&#xD;
             inactive ingredients in Epidiolex)&#xD;
&#xD;
          -  Any radiological evidence of metastatic disease (determined by standard of care&#xD;
             computed tomography [CT] scans of abdomen. pelvis, chest, whole body bone scan or&#xD;
             Axium positron emission tomography scan). Questionable lesions on bone scan will be&#xD;
             confirmed by standard of care methods such as plain X-rays or Axium positron emission&#xD;
             tomography scan, if not previously performed&#xD;
&#xD;
          -  Receipt of prior cytotoxic chemotherapy for recurrent prostate cancer&#xD;
&#xD;
          -  Use of androgen deprivation therapy (for example, bicalutamide, flutamide, nilutamide,&#xD;
             or leuprolide acetate) concurrently or within the previous 3 months.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness such as active infections. Other illnesses will be&#xD;
             evaluated and eligibility status determined at the discretion of the treating&#xD;
             physician and the investigator&#xD;
&#xD;
          -  Psychiatric illness/social situations that would limit compliance with study&#xD;
             requirements&#xD;
&#xD;
          -  Concomitant use of valproate or clobazam&#xD;
&#xD;
          -  Concurrent use of over-the-counter CBD oil, Marinol or marijuana&#xD;
&#xD;
          -  Epidiolex is a moderate inhibitor of CYP2C19 and a moderate/strong inhibitor of&#xD;
             CYP3A4, therefore concurrent use of CYP2C19 substrates is not allowed&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <gender_description>prostate cancer only occurs in male</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Zin W. Myint, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Kentucky</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Markey Cancer Center</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40536</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>June 6, 2020</study_first_submitted>
  <study_first_submitted_qc>June 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>October 7, 2021</last_update_submitted>
  <last_update_submitted_qc>October 7, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 15, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Kentucky</investigator_affiliation>
    <investigator_full_name>Zin W Myint</investigator_full_name>
    <investigator_title>Assistant Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>Prostate</keyword>
  <keyword>Rising PSA</keyword>
  <keyword>CBD Oil</keyword>
  <keyword>Epidiolex</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cannabidiol</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>July 28, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/03/NCT04428203/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <pending_results>
    <submitted>May 12, 2023</submitted>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04428203
org study id: MCC-20-GU-74-PMC
nct id: NCT04428203
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
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.
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
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
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.
measure: Change in serial PSA levels from baseline throughout the treatment period as an indication of biochemical response.
time frame: within 90 days
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
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
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
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
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.
arm group label: single arm
arm group type: Experimental
description: 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
intervention type: Drug
intervention name: Epidiolex Oral Liquid Product
description: 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.
arm group label: single arm
other name: CBD oil
criteria: 
gender: Male
gender based: Yes
gender description: prostate cancer only occurs in male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Zin W. Myint, MD
role: Principal Investigator
affiliation: University of Kentucky
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Kentucky
investigator full name: Zin W Myint
investigator title: Assistant Professor of Medicine
mesh term: Prostatic Neoplasms
mesh term: Cannabidiol
sharing ipd: No
provided document: 
submitted: May 12, 2023