CANNABIDIOL for Breast cancer (early, hormone receptor-positive) | Aromatase inhibitor-associated musculoskeletal pain

Inclusion criteria

• {"criterion_text":"- 1.\tPatient must understand, sign and date the written informed consent form (ICF) prior to any protocol-specific procedures performed. Patient should be able and willing to comply with study visits and procedure as per protocol.\n- 10.\tPatients should report an average joint pain score of ≥ 4 out of 10 on the Brief Pain Inventory (BPI, Appendix 2) within 7 days before registration.\n- 11.\tPatient must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other trial procedures.\n- 12.\tWomen of childbearing potential (CBP), defined as all women physiologically capable of becoming pregnant, must have confirmed negative urine or serum pregnancy test (for β-hCG) within 7 days of randomization.\n- 13.\tWomen of CBP, defined as all women physiologically capable of becoming pregnant, must be willing to use highly effective methods of contraception. It is recommended that sexually active males use a condom during intercourse and it is strongly advised that they do not father a child in this period (a condom is required to be used also by vasectomized men as well as during intercourse with a male partner in order to prevent delivery of the drug via seminal fluid). In all patients, contraception must continue during the trial treatment and for 3 months after stopping it, due to AI treatment. For women, highly effective contraception methods include: a.\tTotal abstinence (when this is in line with the preferred and usual lifestyle of the patient). Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception; b.\tFemale sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least 6 weeks before taking trial treatment. In case of bilateral oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment; c.\tPlacement of an intrauterine device (IUD). Notes: -\tUse of oral (estrogen and progesterone), transdermal, injected or implanted hormonal methods of contraception (as well as hormonal replacement therapy) is not allowed in this trial. -\tWomen are considered of CBP unless: they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (i.e. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks ago.\n- Specific inclusion criteria for CBD use: 14.\tPatient has adequate bone marrow and organ function as defined by the following local laboratory values: a.\tAbsolute neutrophil count (ANC) ≥ 1.5 × 109/L b.\tPlatelets ≥ 100 × 109/L c.\tHemoglobin ≥ 9.0 g/dL d.\tEstimated glomerular filtration rate (eGFR) ≥ 30 mL/min by a Cockcroft-Gault formula. e.\tAlanine transaminase (ALT) ≤ 1.5 × Upper Limit Normal (ULN) f.\tAspartate transaminase (AST) ≤ 1.5 × ULN g.\tTotal serum bilirubin ≤ ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin ≤ 1.5 × ULN in patients with well documented Gilbert’s Syndrome h.\tInternational normalized ratio (INR) ≤ 1.5 (unless the patient is receiving anticoagulants and the INR is within the therapeutic range of intended use for that anticoagulant within 7 days prior to randomization). i.\tPatient must have the following laboratory values within normal limits or corrected to within normal limits with supplements (the local laboratory value should be documented within normal limits after the correction) before randomization: i.\tSodium ii.\tPotassium iii.\tPhosphorus iv.\tMagnesium v.\tTotal Calcium 15.\tStandard 12-lead ECG values defined as the mean of the triplicate ECGs as locally assessed: d.\tQTcF interval (using Fridericia’s correction) at screening < 450 msec e.\tMean resting heart rate 50-90 bpm (determined from the ECG)\n- 2.\tPatient must be affiliated to a social security system or beneficiary of the same.\n- 3.\tPatient is ≥ 18 years-old at the time of study inclusion\n- 4.\tPatient has histologically confirmed invasive Stage I, II, III breast cancer.\n- 5.\tPatient has breast cancer that is positive for ER and/or PgR (nuclear staining of any intensity ≥ 10%)\n- 6.\tPatients should be taking a standard dose of one of the three approved AIs (i.e., anastrozole, exemestane, or letrozole) for at least 21 days, and not more than 36 months before trial registration;\n- 7.\tIf indicated, patient has completed adjuvant and/or neoadjuvant chemotherapy according to the institutional guidelines, prior to randomization.\n- 8.\tIf indicated, patient has completed adjuvant radiotherapy according to the institutional guidelines, prior to randomization.\n- 9.\tPatient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2."}

Exclusion criteria

• {"criterion_text":"- 1.\tPatient with distant metastases of breast cancer beyond regional lymph nodes (M1 disease according to AJCC 8th edition).\n- 10.\tParticipation 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.\n- 11.\tPregnant or breast-feeding (lactating) women or women who plan to become pregnant or breastfeed during the trial.\n- 12.\tPatient 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\n- Specific exclusion criteria for CBD use: 13.\tPatient with a known hypersensitivity to CBD or any of the excipients of CBD 14.\tPrevious serious adverse reaction to any cannabinoid product such as cannabinoid related psychosis, panic attack or delirium. 15.\tRecreational or medicinal cannabis or synthetic cannabinoid-based medications (including Sativex®) within 2 weeks before study entry 16.\tPatient 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.\tPatient takes drugs as clobazam, valproate, or levodopa; 18.\tPatient has previous history of substance abuse or dependance to alchol, opioids, amphetamines, benzodiazepines and other illicit stimulants. 19.\tClinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, including any of the following: a.\tHistory of documented myocardial infarction (MI), angina pectoris, symptomatic pericarditis, or coronary artery bypass graft (CABG) within 6 months prior to trial entry b.\tDocumented cardiomyopathy c.\tPrior history of LVEF <50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) which did not recover before study entry d.\tLong QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: i.\tRisk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia ii.\tConcomitant 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) iii.\t Inability to determine the QTcF interval e.\tClinically 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) f.\tUncontrolled arterial hypertension with systolic blood pressure (SBP) > 160 mmHg\n- 2.\tPatient 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)\n- 3.\tPatient 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\n- 4.\tPatient 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;\n- 5.\tPatient 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;\n- 6.\tPatient has active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.\n- 7.\tPatients with moderate (Child-Pugh B) hepatic impairment or severe (Child-Pugh C) hepatic impairment.\n- 8.\tPatient 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).\n- 9.\tPatient 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."}

Primary endpoints

• {"endpoint_text":"- The primary endpoint is efficacy of CBD on AI-associated pain, measured by the BPI-SF. A one-point difference in BPI average joint pain is considered a minimal important difference and clinically meaningful","definition_or_measurement_approach":"Measured by the Brief Pain Inventory Short Form (BPI-SF); a one-point difference in BPI average joint pain is considered the minimal important and clinically meaningful difference."}

Secondary endpoints

• {"endpoint_text":"- Articular function, stiffness and pain of knees and hips as measured by the Western Ontario and McMaster Universities Osteoarthritis scale (WOMAC) Qol Qol domains will be assessed using: EORTC QLQ-C30 EORTC QLQ-BR45 (Aaronson et al. 1993; Bjelic-Radisic et al. 2020), and the fatigue subscale EORTC QLQ-FA12\n- Anxiety and depression. Anxiety and depression will be assessed using the Hospital Anxiety and Depression Scale (HADS)\n- Adherence : patient’s self-reporting through the questionnaire MIS (medication intake survey), collected at baseline and weeks 4, 12, 13, 17, 25 and 37\n- Safety. A trained research nurse will collect side effects measured by CTCAE V.5. An adverse event (AE) is defined as any untoward medical occurrence, in a patient or clinical trial subject treated by a medicinal product and which does not necessarily have a causal relationship with this treatment. The AE collected will be particularly focused on nausea, constipation, cognitive dysfunction, nervous system and psychiatric side effects. Drug consumption and Hospitalizations associated with nervous system and psychiatric disorders\n- Risk-taking behavior. Information on risk perception and attitude in risk-taking situations will be evaluated with the DOSPERT (Domain-Specific Risk-Taking) scale.\n- Daily pain medication consumption for muskuloskeletal symptoms collected through a daily diary filled in by each participant\n- Drug addiction will be assessed using the CAST questionnaire","definition_or_measurement_approach":"WOMAC for function/stiffness/pain of knees/hips; QoL via EORTC QLQ-C30 and QLQ-BR45 and fatigue subscale QLQ-FA12; Anxiety/depression via HADS; Adherence via MIS questionnaire at specified timepoints; Safety via CTCAE v5 collected by research nurse focused on specified symptoms; Risk-taking via DOSPERT scale; Daily pain medication via participant diary; Drug addiction via CAST questionnaire."}

France

Earliest CTIS Part Ii Submission Date

02-08-2024

Latest Decision Or Authorization Date

06-08-2025

Processing Time Days

369

Number Of Sites

2

Number Of Participants

130

Primary sponsor

Full Name

Institut Gustave Roussy

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France