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.

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

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.

Data can be shared no earlier than 1 year following the date of publication

Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

1 week follow up

it excluded men, so its findings cannot be extrapolated beyond women.