High Cannabidiol Plant Extract (BRC-001) to Improve Aromatase Inhibitor-Induced Arthralgia in Women With Breast Cancer

Inclusion Criteria:

• Documented informed consent of the participant

• Age: ≥ 18 years

• Eastern Cooperative Oncology Group (ECOG) ≤ 2

• Postmenopausal by last menses > 12 months or medically induced menopause inpremenopausal women for AI therapy use

• At least 5 years since other malignancy except adequately treated basal cell orsquamous cell skin cancer, in situ cervical cancer, or adequately treated stage I orII cancer from which the patient is currently in complete remission

• Ability to read and understand English, Spanish, or translations by interpreters forquestionnaires

• Histologically confirmed primary invasive adenocarcinoma of the breast or ductalcarcinoma in situ of the breast

• Stage 0, I, II, or IIIA disease

• No metastatic disease

• Must have undergone definitive breast cancer surgery and recovered

• Must have completed adjuvant chemotherapy as applicable, including systemicchemotherapy, anti-HER2 therapy, and/or radiation therapy

• Estrogen-receptor positive (ER+) and/or progesterone-receptor positive (PR+)

• Currently taking a third-generation aromatase inhibitor (AI) (e.g., anastrozole [Arimidex (registered trademark)], letrozole [Femara (registered trademark)], orexemestane [Aromasin (registered trademark)]) for ≥ 90 days prior to registrationwith plans to continue for ≥ 180 days after registration

• Must have a worst pain/stiffness of ≥ 4 on the Brief Pain Inventory (BPI) (item #2)that has started or increased with AI therapy

Exclusion Criteria:

• < 3 months since prior cannabinoid containing cannabis or hemp products includingCBD, tetrahydrocannabinol (THC), Marinol, and Epidiolex and must agree to refrainfrom use from sources outside of this study

• < 28 days since prior investigational agents

• Medical therapy, alternative therapy, or physical therapy for joint pain/stiffnesswithin the past 30 days

• Narcotic use within 14 days of registration

• Patients may have received corticosteroid treatment; however, the following criteriaapply:

• Patients must not have received oral or intramuscular corticosteroids within 28days prior to registration

• Patients must not have received intra-articular steroids to the study, or anyother, joint within 28 days prior to registration

• Patients must not have received topical analgesics (e.g., capsaicin preparations) tothe study joint or any other analgesics (e.g., opiates, tramadol; with exception ofnonsteroidal anti-inflammatory drugs [NSAIDs] and acetaminophen) within 14 daysprior to registration

• History of bone fracture or surgery of the afflicted hands, knees, and/or otherjoints within 6 months prior to registration

• Any uncontrolled illness including ongoing or active infection

• Known allergies or contraindications to cannabis

• Significantly impaired hepatic function (alanine aminotransferase [ALT] > 5 x upperlimit of normal [ULN] or total bilirubin [TBL] > 2 x ULN) OR the ALT or aspartateaminotransferase (AST) > 3 x ULN and TBL > 2 x ULN (or international normalizedratio [INR] > 1.5

• Grade 3+ renal impairment

• Clinically significant lab abnormalities in ALT, AST, total bilirubin, hemoglobin,hematocrit, or creatinine or any other laboratory tests that in the opinion of theinvestigator would prevent the patient from safely participating in the study

• Having current thoughts of suicide or self-harm or history of suicidal ideation orattempted suicide

• Meeting Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-V)criteria for current major psychiatric illness, such as bipolar disorder, majordepression, or psychosis (including schizophrenia and affective psychosis)

• History of seizure disorder

• Concomitant administration with drugs that may interact adversely with CBD includingwarfarin, theophylline, amiodarone, anti-epileptic (e.g., clobazam, stiripentol,valproate, topiramate), anticonvulsant (e.g., diazepam, lamotrigine, phenytoin,ethosuximide, oxcarbazepine, pregabalin, tigabine, gabapentin); 3) barbiturate (e.g., phenobarbital, hexobarbital), benzodiazepine (e.g, chlordiazepoxide,clonazepam), opioid/narcotic (e.g, codeine, morphine)

• Concomitant administration of cyclin-dependent kinase 4/6 inhibitors, such asabemaciclib, with AI therapy

• Following a physical examination, the patient has any abnormalities that, in theopinion of the investigator would prevent the patient from safely participating inthe study

• Other active malignancy

• Any other condition or medication use that would, in the Investigator's judgment,contraindicate the patient's participation in the clinical study due to safetyconcerns with clinical study procedures

• Participants unwilling to abstain from donation of blood during the study

• Participants who plan to travel outside of the United States during the study period

• Women with childbearing potential are not eligible to participate. The study is forpostmenopausal women taking aromatase inhibitors for adjuvant endocrine therapy

• Participants with cognitive impairment are excluded due to dose titrationinstructions and completion of questionnaires

• Prospective participants who, in the opinion of the investigator, may not be able tocomply with all study procedures (including compliance issues related tofeasibility/logistics)