<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/NCT04482244</url>
  </required_header>
  <id_info>
    <org_study_id>19-886</org_study_id>
    <nct_id>NCT04482244</nct_id>
  </id_info>
  <brief_title>RCT of CBD for Anxiety in Advanced Breast Cancer</brief_title>
  <official_title>Randomized, Double-blind Phase II Study of a Single Dose of Cannabidiol (CBD) for Acute Anticipatory Anxiety in Advanced Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dana-Farber Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hans and Mavis Lopater Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Dana-Farber Cancer Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This research study is investigating use of a single dose of cannabidiol (CBD) to help manage&#xD;
      anticipatory anxiety in participants with advanced breast cancer poised to undergo computed&#xD;
      tomography (CT) or positron emission tomography (PET) to assess tumor burden.&#xD;
&#xD;
      The name of the study drug(s) are:&#xD;
&#xD;
      - Cannabidiol (CBD)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, double-blind, placebo-controlled Phase II trial of a single dose of CBD&#xD;
      for acute anticipatory anxiety in patients with advanced breast cancer undergoing computed&#xD;
      tomography (CT) or positron emission tomography (PET) to assess tumor burden.&#xD;
&#xD;
      The research study investigates use of CBD to manage anxiety prior to an oncologic imaging&#xD;
      scan. CBD is a component of the cannabis sativa (marijuana) plant and of hemp. Studies of CBD&#xD;
      have led to its approval by the Food and Drug Administration for certain childhood seizure&#xD;
      disorders. Researchers have also been studying the use of CBD to manage anxiety and pain.&#xD;
&#xD;
      This study is designed to learn if the drug can help reduce anxiety and can safely be given&#xD;
      to participants with advanced breast cancer who are scheduled for a CT or PET scan.&#xD;
&#xD;
        -  After screening procedures confirm participation in the research study, participants&#xD;
           will be &quot;randomized&quot; into one of two study groups: one group will receive CBD, the other&#xD;
           group will receive a placebo of flavored corn syrup.&#xD;
&#xD;
        -  Randomization means that participants are put into a group by chance. Neither the&#xD;
           participant nor the research team will choose participant group assignment.&#xD;
&#xD;
             -  Participants will have a 66% chance of receiving a single dose of CBD.&#xD;
&#xD;
             -  Participants will have a 33% chance of receiving a single dose of placebo.&#xD;
&#xD;
        -  On the day of treatment, participants will complete questionnaires before and after&#xD;
           receiving a single dose of CBD or placebo then undergo computed tomography (CT) scan or&#xD;
           positron emission tomography (PET). Participants will be contacted by phone&#xD;
           approximately a week later and interviewed about study drug consumption and the CT/PET&#xD;
           scan experience.&#xD;
&#xD;
      This study is supported by funding from the Hans and Mavis Lopater Foundation.&#xD;
&#xD;
      Approximately 50 people are anticipated to take part in this study.&#xD;
&#xD;
      This research study is a Phase II clinical trial. Phase II clinical trials test the safety&#xD;
      and effectiveness of an investigational drug to learn whether the drug works in treating a&#xD;
      specific disease. &quot;Investigational&quot; means that the drug is being studied. The FDA (the U.S.&#xD;
      Food and Drug Administration) has not approved CBD to manage anxiety but it has been approved&#xD;
      for use in children with some seizure disorders.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 19, 2022</start_date>
  <completion_date type="Anticipated">February 18, 2024</completion_date>
  <primary_completion_date type="Actual">June 18, 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Anxiety Score-Visual Analog Mood Scale (VAMs) anxiety subscale,</measure>
    <time_frame>1 day of the drug administration pre-dose (T2) and 3 +/- 1 hour after drug administration (T3) up to 1 day</time_frame>
    <description>The change in anxiety score will be calculated for each patient and a Wilcoxon rank sum test will be used to assess whether the change score is different among patients randomized to CBD as compared to placebo.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment-Related Adverse Events (PRO-CTCAE™) 5.</measure>
    <time_frame>1 day of the drug administration pre-dose (T2) and 3 +/- 1 hour after drug administration (T3) up to 1 weeks post ingestion</time_frame>
    <description>Measured using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE™) and a qualitative assessment, patient-reported side effects and acceptability of taking oral CBD (versus placebo) for managing anticipatory anxiety.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mood Changes</measure>
    <time_frame>Baseline through 3 +/- 1 hour after drug administration (T3) up to 1 day</time_frame>
    <description>Measured by VAMS subscales-The Visual Analog Mood Scale (VAMS) a validated in-the-moment measure of eight specific mood states: Afraid, Confused, Sad, Angry, Energetic, Tired, Happy, and Tense. Subjects are asked to mark their mood along this continuum. The measure is scored using a metric ruler</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Nausea Rate</measure>
    <time_frame>Baseline through 3 +/- 1 hour after drug administration (T3) up to 1 week</time_frame>
    <description>Measured by the European Organisation for Research and Treatment of Cancer core quality of life questionnaire-nausea subscale.&#xD;
The EORTC-QLQc30 is a widely used and validated measure of symptom burden.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain Rate</measure>
    <time_frame>Baseline through 3 +/- 1 hour after drug administration (T3) up to 1 day</time_frame>
    <description>Pain levels (as measured by the PEG) 3 +/- 1 hour after study agent administration in patients with advanced cancer.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Numeric Pain Rating Scale (NPRS)</measure>
    <time_frame>Baseline , 1 day of the drug administration pre-dose</time_frame>
    <description>pain intensity scale is scored from 0 to 10 (with 10 representing &quot;worst possible&quot; pain).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Advanced Breast Cancer</condition>
  <condition>Anxiety</condition>
  <condition>CBD</condition>
  <arm_group>
    <arm_group_label>Cannabidiol</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After screening procedures confirm participation in the research study, participants will be randomized one of two groups:&#xD;
Participants in the experimental arm will complete questionnaires and then receive a single dose of CBD prior to diagnostic CT scan or positron emission tomography (PET) .&#xD;
Cannabidiol: Oral, per protocol dosage, single dose&#xD;
Additional questionnaires 2 hours post scan and follow up via phone call 1 week regarding experience</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>After the screening procedures confirm participation in the research study, participants will be randomized one of two groups:&#xD;
Participants in the placebo arm will complete questionnaire and then receive a single dose of placebo prior to diagnostic CT scan or positron emission tomography (PET) .&#xD;
Placebo: Oral, per protocol dosage, single dose&#xD;
Additional questionnaires 2 hours post scan and follow up via phone call 1 week regarding experience</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cannabidiol</intervention_name>
    <description>Liquid taken orally</description>
    <arm_group_label>Cannabidiol</arm_group_label>
    <other_name>Epidiolex</other_name>
    <other_name>CBD</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Liquid taken orally</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of Stage IV or metastatic breast cancer&#xD;
&#xD;
          -  Age ≥18 years.&#xD;
&#xD;
          -  ECOG performance status ≤2 (Karnofsky ≥60%).&#xD;
&#xD;
          -  Participants must have adequate organ and marrow function at baseline as defined&#xD;
             below:&#xD;
&#xD;
               -  total bilirubin &gt;2 times institutional upper limit of normal (ULN)&#xD;
&#xD;
               -  AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN&#xD;
&#xD;
               -  Baseline anxiety as measured by GAD-7 ≥5&#xD;
&#xD;
          -  At least mild anxiety typically experienced prior to oncologic scans (as measured by a&#xD;
             prescreen survey item)&#xD;
&#xD;
               -  Computed tomography (CT) or positron emission tomography (PET) to assess tumor&#xD;
                  burden scheduled for within 48 hours of study drug administration&#xD;
&#xD;
               -  No cannabis, delta-9-tetrahydrocannabinol or cannabidiol use within 24-hours of&#xD;
                  study drug administration.&#xD;
&#xD;
          -  No benzodiazepine consumption within 8 hours of study drug administration&#xD;
             (e.g.,nighttime benzodiazepine use permissible)&#xD;
&#xD;
          -  No driving for 12 hours following study drug administration.&#xD;
&#xD;
          -  English proficiency&#xD;
&#xD;
          -  The effects of cannabidiol (Epidiolex) on the developing human fetus are unknown. For&#xD;
             this reason and because cannabis is known to be teratogenic, women of child-bearing&#xD;
             potential must test as nonpregnant prior to entering the study. The study team will&#xD;
             encourage women of child-bearing age and men to use adequate contraception (hormonal&#xD;
             or barrier method of birth control; abstinence) prior to study entry and for the&#xD;
             duration of study participation. Should a woman become pregnant or suspect she is&#xD;
             pregnant while she or her partner is participating in this study, she should inform&#xD;
             her treating physician immediately. Men treated or enrolled on this protocol must also&#xD;
             agree to use adequate contraception prior to the study, for the duration of study&#xD;
             participation, and for 1 week after cannabidiol (Epidiolex) consumption. Women either&#xD;
             age &gt; 54 years or documented to be in menopause or status post hysterectomy will not&#xD;
             be required to obtain bHCG.&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to cannabidiol (Epidiolex) or placebo (which contains sesame, corn and&#xD;
             gluten)&#xD;
&#xD;
          -  History of current clobazam or valproic acid use&#xD;
&#xD;
          -  Current uncontrolled illness, for instance sepsis, symptomatic congestive heart&#xD;
             failure, unstable angina pectoris, cardiac arrhythmia&#xD;
&#xD;
          -  Current use of antiretroviral therapy&#xD;
&#xD;
          -  Participants with psychiatric illness or social situations that would limit compliance&#xD;
             with study requirements&#xD;
&#xD;
          -  Current hepatocellular carcinoma, or documented history of difficult to control&#xD;
             diabetes -- Active participation in a clinical drug trial&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ilana Braun, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dana-Farber Cancer Institute</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ilana Braun, MD</last_name>
    <phone>(617) 643-0576</phone>
    <email>ibraun@partners.org</email>
  </overall_contact>
  <location>
    <facility>
      <name>Dana Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ilana M Braun, MD</last_name>
      <phone>617-643-0576</phone>
      <email>Ibraun@partners.org</email>
    </contact>
    <contact_backup>
      <last_name>Manan M Nayak, PhD</last_name>
      <phone>617-632-5096</phone>
      <email>manan_nayak@dfci.harvard.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Ilana M Braun, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>William F Pirl, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Peter R Chai, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Manan M Nayak, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Stephanie Tung, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>July 20, 2020</study_first_submitted>
  <study_first_submitted_qc>July 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 22, 2020</study_first_posted>
  <last_update_submitted>August 21, 2023</last_update_submitted>
  <last_update_submitted_qc>August 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Dana-Farber Cancer Institute</investigator_affiliation>
    <investigator_full_name>Ilana Braun, MD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Advanced Breast Cancer</keyword>
  <keyword>Anxiety</keyword>
  <keyword>CBD</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Anxiety Disorders</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>Yes</sharing_ipd>
    <ipd_description>The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>Data can be shared no earlier than 1 year following the date of publication</ipd_time_frame>
    <ipd_access_criteria>Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu</ipd_access_criteria>
  </patient_data>
  <!-- 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/NCT04482244
org study id: 19-886
nct id: NCT04482244
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This research study is investigating use of a single dose of cannabidiol (CBD) to help manage
      anticipatory anxiety in participants with advanced breast cancer poised to undergo computed
      tomography (CT) or positron emission tomography (PET) to assess tumor burden.

      The name of the study drug(s) are:

      - Cannabidiol (CBD)
This is a randomized, double-blind, placebo-controlled Phase II trial of a single dose of CBD
      for acute anticipatory anxiety in patients with advanced breast cancer undergoing computed
      tomography (CT) or positron emission tomography (PET) to assess tumor burden.

      The research study investigates use of CBD to manage anxiety prior to an oncologic imaging
      scan. CBD is a component of the cannabis sativa (marijuana) plant and of hemp. Studies of CBD
      have led to its approval by the Food and Drug Administration for certain childhood seizure
      disorders. Researchers have also been studying the use of CBD to manage anxiety and pain.

      This study is designed to learn if the drug can help reduce anxiety and can safely be given
      to participants with advanced breast cancer who are scheduled for a CT or PET scan.

        -  After screening procedures confirm participation in the research study, participants
           will be "randomized" into one of two study groups: one group will receive CBD, the other
           group will receive a placebo of flavored corn syrup.

        -  Randomization means that participants are put into a group by chance. Neither the
           participant nor the research team will choose participant group assignment.

             -  Participants will have a 66% chance of receiving a single dose of CBD.

             -  Participants will have a 33% chance of receiving a single dose of placebo.

        -  On the day of treatment, participants will complete questionnaires before and after
           receiving a single dose of CBD or placebo then undergo computed tomography (CT) scan or
           positron emission tomography (PET). Participants will be contacted by phone
           approximately a week later and interviewed about study drug consumption and the CT/PET
           scan experience.

      This study is supported by funding from the Hans and Mavis Lopater Foundation.

      Approximately 50 people are anticipated to take part in this study.

      This research study is a Phase II clinical trial. Phase II clinical trials test the safety
      and effectiveness of an investigational drug to learn whether the drug works in treating a
      specific disease. "Investigational" means that the drug is being studied. The FDA (the U.S.
      Food and Drug Administration) has not approved CBD to manage anxiety but it has been approved
      for use in children with some seizure disorders.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change in Anxiety Score-Visual Analog Mood Scale (VAMs) anxiety subscale,
time frame: 1 day of the drug administration pre-dose (T2) and 3 +/- 1 hour after drug administration (T3) up to 1 day
description: The change in anxiety score will be calculated for each patient and a Wilcoxon rank sum test will be used to assess whether the change score is different among patients randomized to CBD as compared to placebo.
measure: Number of Participants With Treatment-Related Adverse Events (PRO-CTCAE™) 5.
time frame: 1 day of the drug administration pre-dose (T2) and 3 +/- 1 hour after drug administration (T3) up to 1 weeks post ingestion
description: Measured using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE™) and a qualitative assessment, patient-reported side effects and acceptability of taking oral CBD (versus placebo) for managing anticipatory anxiety.
measure: Mood Changes
time frame: Baseline through 3 +/- 1 hour after drug administration (T3) up to 1 day
description: Measured by VAMS subscales-The Visual Analog Mood Scale (VAMS) a validated in-the-moment measure of eight specific mood states: Afraid, Confused, Sad, Angry, Energetic, Tired, Happy, and Tense. Subjects are asked to mark their mood along this continuum. The measure is scored using a metric ruler
measure: Nausea Rate
time frame: Baseline through 3 +/- 1 hour after drug administration (T3) up to 1 week
description: Measured by the European Organisation for Research and Treatment of Cancer core quality of life questionnaire-nausea subscale.
The EORTC-QLQc30 is a widely used and validated measure of symptom burden.
measure: Pain Rate
time frame: Baseline through 3 +/- 1 hour after drug administration (T3) up to 1 day
description: Pain levels (as measured by the PEG) 3 +/- 1 hour after study agent administration in patients with advanced cancer.
measure: Numeric Pain Rating Scale (NPRS)
time frame: Baseline , 1 day of the drug administration pre-dose
description: pain intensity scale is scored from 0 to 10 (with 10 representing "worst possible" pain).
arm group label: Cannabidiol
arm group type: Experimental
description: After screening procedures confirm participation in the research study, participants will be randomized one of two groups:
Participants in the experimental arm will complete questionnaires and then receive a single dose of CBD prior to diagnostic CT scan or positron emission tomography (PET) .
Cannabidiol: Oral, per protocol dosage, single dose
Additional questionnaires 2 hours post scan and follow up via phone call 1 week regarding experience
arm group label: Placebo
arm group type: Placebo Comparator
description: After the screening procedures confirm participation in the research study, participants will be randomized one of two groups:
Participants in the placebo arm will complete questionnaire and then receive a single dose of placebo prior to diagnostic CT scan or positron emission tomography (PET) .
Placebo: Oral, per protocol dosage, single dose
Additional questionnaires 2 hours post scan and follow up via phone call 1 week regarding experience
intervention type: Drug
intervention name: Cannabidiol
description: Liquid taken orally
arm group label: Cannabidiol
other name: Epidiolex
other name: CBD
intervention type: Other
intervention name: Placebo
description: Liquid taken orally
arm group label: Placebo
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ilana Braun, MD
role: Principal Investigator
affiliation: Dana-Farber Cancer Institute
last name: Ilana Braun, MD
phone: (617) 643-0576
email: ibraun@partners.org
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Dana-Farber Cancer Institute
investigator full name: Ilana Braun, MD
investigator title: Principal Investigator
mesh term: Breast Neoplasms
mesh term: Anxiety Disorders
mesh term: Cannabidiol
sharing ipd: Yes
ipd description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: Data can be shared no earlier than 1 year following the date of publication
ipd access criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu