Study Assessing the Efficacy and Safety of cANnabidiol Oral Solution for Joint Pain of Adjuvant enDOcrine theRApy in Patients With Early Breast Cancer

1. Patient with distant metastases of breast cancer beyond regional lymph nodes (M1 disease according to AJCC 8th edition).

2. Patient has not recovered from clinical and laboratory acute toxicities of chemotherapy, radiotherapy and/or surgery (i.e. patient has toxicities attributed to prior anti-neoplastic therapy NCI CTCAE version 5.0 grade ≥1 at day of randomization, excluding alopecia and amenorrhea)

3. Patient has a concurrent invasive malignancy or a prior invasive malignancy whose treatment was completed within 2 years before ICF signature. Note: Patients with prior or concurrent in situ malignancies are eligible provided that adequate curative treatment is completed prior to randomization

4. Patient has previous history of bone fracture or surgery of the affected knees, hands or both within 6 months prior to enrolment or known rheumatologic diseases;

5. Patient has received opioids analgesics, systemic NSAIDs, topical analgesics, oral, intra-articular or intramuscular corticosteroids for treatment of joint pain or joint stiffness within 28 days prior registration;

6. Patient has active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.

7. Patients with moderate (Child-Pugh B) hepatic impairment or severe (Child-Pugh C) hepatic impairment.

8. Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the oral trial treatments (e.g. uncontrolled ulcerative diseases, uncontrolled nausea, vomiting or diarrhea, malabsorption syndrome, or small bowel resection).

9. Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the Investigators judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical trial or compromise compliance with the protocol (e.g. chronic pancreatitis, chronic active hepatitis, liver cirrhosis or any other significant liver disease, active untreated or uncontrolled fungal, bacterial or viral infections, active infection requiring systemic anti-bacterial therapy, etc.) or limit life expectancy to ≤5 years.

10. Participation in a prior interventional study and received trial treatment with an investigational product (or used an investigational device) within 30 days prior to randomization or within 5 half-lives of the investigational product, whichever is longer.

11. Pregnant or breast-feeding (lactating) women or women who plan to become pregnant or breastfeed during the trial.

12. Patient under guardianship or deprived of his liberty by a judicial or administrative decision or under justice protection or under curatorship or unable of giving his consent

13. Patient with a known hypersensitivity to CBD or any of the excipients of CBD

14. Previous serious adverse reaction to any cannabinoid product such as cannabinoid related psychosis, panic attack or delirium.

15. Recreational or medicinal cannabis or synthetic cannabinoid based medications (including Sativex®) within 2 weeks before study entry

16. Patient has previous or active psychological, psychiatric or central nervous system disorders, including epilepsy; schizophrenia or any other psychosis, severe borderline personality, patient with significant suicidal ideation.

17. Patient takes drugs as clobazam, valproate, or levodopa;

18. Patient has previous history of substance abuse or dependence to alcohol, opioids, amphetamines, benzodiazepines and other illicit stimulants.

19. Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, including any of the following:

1. History of documented myocardial infarction (MI), angina pectoris, symptomatic pericarditis, or coronary artery bypass graft (CABG) within 6 months prior to trial entry

2. Documented cardiomyopathy

3. Prior history of LVEF \<50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) which did not recover before study entry

4. Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:

* Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia

* Concomitant medication(s) with a known risk to prolong the QT interval and/or known to cause TdP that cannot be discontinued or replaced by safe alternative medication (e.g. within 5 half-lives or 7 days prior to starting trial treatment)

* Inability to determine the QTcF interval

5. Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade Atrioventricular (AV) block (e.g. bifascicular block, Mobitz type II and third degree AV block)

6. Uncontrolled arterial hypertension with systolic blood pressure (SBP) \> 160 mmHg

What this study is about