RCT of CBD for Anxiety in Advanced Breast Cancer

Study Overview
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Brief Summary
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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)

Detailed Description
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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.

Official Title
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Randomized, Double-blind Phase II Study of a Single Dose of Cannabidiol (CBD) for Acute Anticipatory Anxiety in Advanced Breast Cancer

Conditions
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Advanced Breast Cancer, Anxiety, CBD

Intervention / Treatment
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* Drug: Cannabidiol
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Stage IV or metastatic breast cancer Age ≥18 years. ECOG performance status ≤2 (Karnofsky ≥60%). Participants must have adequate organ and marrow function at baseline as defined below: total bilirubin >2 times institutional upper limit of normal (ULN) AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN Baseline anxiety as measured by GAD-7 ≥5 At least mild anxiety typically experienced prior to oncologic scans (as measured by a prescreen survey item) Computed tomography (CT) or positron emission tomography (PET) to assess tumor burden scheduled for within 48 hours of study drug administration No cannabis, delta-9-tetrahydrocannabinol or cannabidiol use within 24-hours of study drug administration. No benzodiazepine consumption within 8 hours of study drug administration (e.g.,nighttime benzodiazepine use permissible) No driving for 12 hours following study drug administration. English proficiency The effects of cannabidiol (Epidiolex) on the developing human fetus are unknown. For this reason and because cannabis is known to be teratogenic, women of child-bearing potential must test as nonpregnant prior to entering the study. The study team will encourage women of child-bearing age and men to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 1 week after cannabidiol (Epidiolex) consumption. Women either age > 54 years or documented to be in menopause or status post hysterectomy will not be required to obtain bHCG. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: History of allergic reactions attributed to compounds of similar chemical or biologic composition to cannabidiol (Epidiolex) or placebo (which contains sesame, corn and gluten) History of current clobazam or valproic acid use Current uncontrolled illness, for instance sepsis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia Current use of antiretroviral therapy Participants with psychiatric illness or social situations that would limit compliance with study requirements Current hepatocellular carcinoma, or documented history of difficult to control diabetes -- Active participation in a clinical drug trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cannabidiol<br>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 | Drug: Cannabidiol<br>* Liquid taken orally<br>* Other names: CBD;|
| Placebo Comparator: Placebo<br>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 | Other: Placebo<br>* Liquid taken orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Anxiety Score-Visual Analog Mood Scale (VAMs) anxiety subscale, | 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. | 1 day of the drug administration pre-dose (T2) and 3 +/- 1 hour after drug administration (T3) up to 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Related Adverse Events (PRO-CTCAE™) 5. | 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. | 1 day of the drug administration pre-dose (T2) and 3 +/- 1 hour after drug administration (T3) up to 1 weeks post ingestion | 
| Mood Changes | 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 | Baseline through 3 +/- 1 hour after drug administration (T3) up to 1 day | 
| Nausea Rate | 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. | Baseline through 3 +/- 1 hour after drug administration (T3) up to 1 week | 
| Pain Rate | Pain levels (as measured by the PEG) 3 +/- 1 hour after study agent administration in patients with advanced cancer. | Baseline through 3 +/- 1 hour after drug administration (T3) up to 1 day | 
| Numeric Pain Rating Scale (NPRS) | pain intensity scale is scored from 0 to 10 (with 10 representing worst possible pain). | Baseline , 1 day of the drug administration pre-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Breast Cancer, Anxiety, CBD