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

High Cannabidiol (CBD) Standardized Extract for Aromatase Inhibitor-Induced Arthralgia - A Randomized Controlled Double Blind Clinical Trial

This phase II trial tests the effectiveness of cannabidiol (CBD) plant extract (BRC-001) in improving joint stiffness and pain (arthralgia) in women with breast cancer taking aromatase inhibitors (AIs). AIs lower blood levels of estrogen in postmenopausal women to reduce breast cancer recurrence. Women on AI therapy may experience joint stiffness, pain and arthritis symptoms as a side effect of the medication. Some women stop AI therapy due to these side effects and do not receive the maximum benefit from the medication. CBD is derived from the same plant family as marijuana but is not associated with a "high" or mind-altering effect and is not habit-forming. Research in animals and humans indicates that CBD might decrease inflammation in joint tissues and may help reduce chronic pain in ailments such as arthritis. BRC-001 may reduce joint pain in women with breast cancer taking AIs.

PRIMARY OBJECTIVE:

I. To assess the preliminary efficacy of BRC-001 versus placebo by change in Brief Pain Inventory-Short Form (BPI-SF) worst pain severity scores from 0 to 3 months.

SECONDARY OBJECTIVES:

I. To evaluate indicators of preliminary efficacy of BRC-001 on joint symptoms of pain and stiffness assessed by BPI-SF total pain severity and total pain interference scores and Visual Analog Scale-Pain.

II. To evaluate tolerability by adverse events, anxiety by Patient Reported Outcomes Measurement Information System (PROMIS) Emotional Distress-Anxiety Short Form (SF) 6a, sleep by PROMIS Sleep Disturbance SF 4a, quality of life by Functional Assessment of Cancer Therapy-Endocrine System (FACT-ES).

III. To evaluate safety by clinical laboratory tests (alanine aminotransferase [ALT], aspartate aminotransferase [AST], total bilirubin).

IV. To evaluate changes in physical function by dynamometer measurements of grip strength.

EXPLORATORY OBJECTIVES:

I. To evaluate blood-based biomarkers related to aromatase inhibitor-induced arthralgia (AIIA) and BRC-001 versus (vs) placebo.

II. Pharmacokinetics of BRC-001.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive BRC-001 orally (PO) twice daily (BID) for up to 3 months. Patients also undergo blood sample collection on study.

ARM II: Patients receive placebo PO BID for up to 3 months. Patients also undergo blood sample collection on study.

After completion of study treatment, patients are followed up at 30 days.

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 in premenopausal women for AI therapy use

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

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

• Histologically confirmed primary invasive adenocarcinoma of the breast or ductal carcinoma 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 systemic chemotherapy, 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)], or exemestane [Aromasin (registered trademark)]) for ≥ 90 days prior to registration with 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 including CBD, tetrahydrocannabinol (THC), Marinol, and Epidiolex and must agree to refrain from use from sources outside of this study

• < 28 days since prior investigational agents

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

• Narcotic use within 14 days of registration

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

  • Patients must not have received oral or intramuscular corticosteroids within 28 days prior to registration
  • Patients must not have received intra-articular steroids to the study, or any other, joint within 28 days prior to registration

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

• History of bone fracture or surgery of the afflicted hands, knees, and/or other joints 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 upper limit of normal [ULN] or total bilirubin [TBL] > 2 x ULN) OR the ALT or aspartate aminotransferase (AST) > 3 x ULN and TBL > 2 x ULN (or international normalized ratio [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 the investigator would prevent the patient from safely participating in the study

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

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

• History of seizure disorder

• Concomitant administration with drugs that may interact adversely with CBD including warfarin, 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 as abemaciclib, with AI therapy

• Following a physical examination, the patient has any abnormalities that, in the opinion of the investigator would prevent the patient from safely participating in the 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 safety concerns 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 for postmenopausal women taking aromatase inhibitors for adjuvant endocrine therapy

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

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