Advanced Breast Cancer, Anxiety, CBD
Conditions
Keywords
Advanced Breast Cancer, Anxiety, CBD
Brief summary
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
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.
Interventions
DRUGCannabidiol
Liquid taken orally
OTHERPlacebo
Liquid taken orally
Sponsors
Dana-Farber Cancer Institute
Hans and Mavis Lopater Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Anxiety Score-Visual Analog Mood Scale (VAMs) Anxiety Subscale | 1 day of the drug administration pre-dose (T2) and 3 +/- 1 hour after drug administration (T3) up to 1 day | Afraid is a negative mood subscale on the VAMS. Each subscale involves a 0 (neutral face or lack of endorsement) to 100 mm (mood face of extreme endorsement) a horizontal line with each pole having an associated mood descriptor. A raw score is a measure of distance from the neutral face (0 mm) to where the participant marks their mood to be in the moment. A linear transformation of a raw score is converted to a T-score and calculated to have a mean of 50 and an SD of 10. The manual provides a T-score conversion table based on sex and age bracket (18-54 years and 55-94 years). A 20T-score (+/-) difference in either direction between a pre- and posttest scores is interpreted as a reliable change in mood, and those differing by more than 30T-score (+/-) is interpreted as both a reliable and a clinically significant relevant threshold for change in mood. A change score for a given mood was calculated based on using T-scores of post-drug administration minus the pre-drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Related Adverse Events (PRO-CTCAE™) 5. | 1 day of the drug administration pre-dose (T2) and 3 +/- 1 hour after drug administration (T3) up to 1 weeks post ingestion | 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. |
| Change in Mood Score-Visual Analog Mood Scale (VAMs) Anxiety Subscale | Baseline through 3 +/- 1 hour after drug administration (T3) up to 1 day | Confused, Sad, Angry, Tired, Tense are negative moods and Energetic and Happy are positive moods on VAMS. Each subscale involves a 0 (neutral face) to 100 mm (mood face) a horizontal line with each pole having an associated mood descriptor. A raw score is a measure of distance from the neutral face (0 mm) to where the participant marks their mood to be in the moment. A linear transformation of a raw score is converted to a T-score and calculated to have a mean of 50 and SD of 10. The manual provides a T-score conversion table based on sex and age bracket (18-54 years and 55-94 years). A 20T-score (+/-) difference in either direction between a pre- and posttest scores is interpreted as a reliable change in mood, and those differing by more than 30T-score (+/-) is interpreted as both a reliable and a clinically significant relevant threshold for change in mood. A change score for a given mood was calculated based on using T-scores of post-drug administration minus the pre-drug. |
| Nausea Rate | Baseline through 3 +/- 1 hour after drug administration (T3) up to 1 week | Nausea and vomiting were measured using two items. Scale scores were calculated by averaging items within scales and transforming average scores linearly. All of the scales range in score from 0 to 100. A high score for a symptom scale or item represents a high level of symptomatology or problems. |
| Numeric Pain Rating Scale (NPRS) | Baseline , 1 day of the drug administration pre-dose | pain intensity scale is scored from 0 to 10 (with 10 representing "worst possible" pain). |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORIlana Braun, MD
Dana-Farber Cancer Institute
Participant flow
Recruitment details
At the cancer center, medical records were screened between November 2, 2021, and March 1, 2023, and obtained physician approval prior to contacting potential participants. Interested women were consented and completed the survey and laboratory assessments necessary to determine eligibility. Survey assessments included demographics, cannabis history, the validated GAD-7 scale, and history of scan-related anxiety.
Pre-assignment details
501 screened. 310 excluded: 76 on clinical drug trial, 64 not responding, 37 declined,133 excluded for other reasons. Of 191 meeting eligibility, 54 without scheduled scan, 40 had scan too soon, 27 denied anxiety, & 3 excluded for other reasons. 67 scheduled for consent: 3 lost interest, 3 denied anxiety, & 1 did not attend. 60 patients consented, but 10 were not randomized, because they didn't meet eligibility criteria. 50 total participants were eligible, consented and randomized.
Participants by arm
| Arm | Count |
|---|---|
| Cannabidiol 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
Cannabidiol: Liquid taken orally | 25 |
| Placebo 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
Placebo: Liquid taken orally | 25 |
| Total | 50 |
Baseline characteristics
| Characteristic | Placebo | Total | Cannabidiol |
|---|---|---|---|
| Age, Continuous | 57 years | 58 years | 60 years |
| baseline anxiety score Mild to moderate | 22 participants | 44 participants | 22 participants |
| baseline anxiety score Severe | 3 participants | 6 participants | 3 participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Black of African American | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Declined | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Multiracial | 2 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 19 Participants | 43 Participants | 24 Participants |
| Region of Enrollment United States | 25 participants | 50 participants | 25 participants |
| Sex: Female, Male Female | 25 Participants | 50 Participants | 25 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 25 |
| other Total, other adverse events | 2 / 25 | 0 / 25 |
| serious Total, serious adverse events | 0 / 25 | 0 / 25 |
Outcome results
Primary
Change in Anxiety Score-Visual Analog Mood Scale (VAMs) Anxiety Subscale
Afraid is a negative mood subscale on the VAMS. Each subscale involves a 0 (neutral face or lack of endorsement) to 100 mm (mood face of extreme endorsement) a horizontal line with each pole having an associated mood descriptor. A raw score is a measure of distance from the neutral face (0 mm) to where the participant marks their mood to be in the moment. A linear transformation of a raw score is converted to a T-score and calculated to have a mean of 50 and an SD of 10. The manual provides a T-score conversion table based on sex and age bracket (18-54 years and 55-94 years). A 20T-score (+/-) difference in either direction between a pre- and posttest scores is interpreted as a reliable change in mood, and those differing by more than 30T-score (+/-) is interpreted as both a reliable and a clinically significant relevant threshold for change in mood. A change score for a given mood was calculated based on using T-scores of post-drug administration minus the pre-drug.
Time frame: 1 day of the drug administration pre-dose (T2) and 3 +/- 1 hour after drug administration (T3) up to 1 day
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cannabidiol | Change in Anxiety Score-Visual Analog Mood Scale (VAMs) Anxiety Subscale | -19.1 T-Score | Standard Deviation 15.4 |
| Placebo | Change in Anxiety Score-Visual Analog Mood Scale (VAMs) Anxiety Subscale | -15.0 T-Score | Standard Deviation 10.9 |
Secondary
Change in Mood Score-Visual Analog Mood Scale (VAMs) Anxiety Subscale
Confused, Sad, Angry, Tired, Tense are negative moods and Energetic and Happy are positive moods on VAMS. Each subscale involves a 0 (neutral face) to 100 mm (mood face) a horizontal line with each pole having an associated mood descriptor. A raw score is a measure of distance from the neutral face (0 mm) to where the participant marks their mood to be in the moment. A linear transformation of a raw score is converted to a T-score and calculated to have a mean of 50 and SD of 10. The manual provides a T-score conversion table based on sex and age bracket (18-54 years and 55-94 years). A 20T-score (+/-) difference in either direction between a pre- and posttest scores is interpreted as a reliable change in mood, and those differing by more than 30T-score (+/-) is interpreted as both a reliable and a clinically significant relevant threshold for change in mood. A change score for a given mood was calculated based on using T-scores of post-drug administration minus the pre-drug.
Time frame: Baseline through 3 +/- 1 hour after drug administration (T3) up to 1 day
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cannabidiol | Change in Mood Score-Visual Analog Mood Scale (VAMs) Anxiety Subscale | Energetic | -1.8 T-Score | Standard Deviation 8.7 |
| Cannabidiol | Change in Mood Score-Visual Analog Mood Scale (VAMs) Anxiety Subscale | Confused | 0.9 T-Score | Standard Deviation 6.7 |
| Cannabidiol | Change in Mood Score-Visual Analog Mood Scale (VAMs) Anxiety Subscale | Tired | -2.0 T-Score | Standard Deviation 9.8 |
| Cannabidiol | Change in Mood Score-Visual Analog Mood Scale (VAMs) Anxiety Subscale | Angry | -3.6 T-Score | Standard Deviation 8.8 |
| Cannabidiol | Change in Mood Score-Visual Analog Mood Scale (VAMs) Anxiety Subscale | Happy | 3.3 T-Score | Standard Deviation 8.7 |
| Cannabidiol | Change in Mood Score-Visual Analog Mood Scale (VAMs) Anxiety Subscale | Tense | -11.6 T-Score | Standard Deviation 12.6 |
| Cannabidiol | Change in Mood Score-Visual Analog Mood Scale (VAMs) Anxiety Subscale | Sad | -5.8 T-Score | Standard Deviation 11.2 |
| Placebo | Change in Mood Score-Visual Analog Mood Scale (VAMs) Anxiety Subscale | Tense | -10.4 T-Score | Standard Deviation 8.8 |
| Placebo | Change in Mood Score-Visual Analog Mood Scale (VAMs) Anxiety Subscale | Confused | -0.1 T-Score | Standard Deviation 4.9 |
| Placebo | Change in Mood Score-Visual Analog Mood Scale (VAMs) Anxiety Subscale | Sad | -8.9 T-Score | Standard Deviation 11.4 |
| Placebo | Change in Mood Score-Visual Analog Mood Scale (VAMs) Anxiety Subscale | Angry | -6.1 T-Score | Standard Deviation 10.5 |
| Placebo | Change in Mood Score-Visual Analog Mood Scale (VAMs) Anxiety Subscale | Energetic | -2.1 T-Score | Standard Deviation 13.6 |
| Placebo | Change in Mood Score-Visual Analog Mood Scale (VAMs) Anxiety Subscale | Tired | -3.6 T-Score | Standard Deviation 10.1 |
| Placebo | Change in Mood Score-Visual Analog Mood Scale (VAMs) Anxiety Subscale | Happy | 2.6 T-Score | Standard Deviation 9.3 |
Secondary
Nausea Rate
Nausea and vomiting were measured using two items. Scale scores were calculated by averaging items within scales and transforming average scores linearly. All of the scales range in score from 0 to 100. A high score for a symptom scale or item represents a high level of symptomatology or problems.
Time frame: Baseline through 3 +/- 1 hour after drug administration (T3) up to 1 week
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cannabidiol | Nausea Rate | NV Score Pre-drug | 6.0 score on a scale | Standard Deviation 8.2 |
| Cannabidiol | Nausea Rate | NV Score Post-drug | 7.3 score on a scale | Standard Deviation 15.3 |
| Placebo | Nausea Rate | NV Score Post-drug | 1.3 score on a scale | Standard Deviation 4.6 |
| Placebo | Nausea Rate | NV Score Pre-drug | 6.7 score on a scale | Standard Deviation 13.6 |
Secondary
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.
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cannabidiol | Number of Participants With Treatment-Related Adverse Events (PRO-CTCAE™) 5. | 2 Participants |
| Placebo | Number of Participants With Treatment-Related Adverse Events (PRO-CTCAE™) 5. | 0 Participants |
Secondary
Numeric Pain Rating Scale (NPRS)
pain intensity scale is scored from 0 to 10 (with 10 representing worst possible pain).
Time frame: Baseline , 1 day of the drug administration pre-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cannabidiol | Numeric Pain Rating Scale (NPRS) | -0.88 score on a scale | Standard Deviation 1.45 |
| Placebo | Numeric Pain Rating Scale (NPRS) | -0.88 score on a scale | Standard Deviation 1.33 |