AI-related Musculoskeletal Pain, Breast Cancer Stage I, Breast Cancer Stage II, Breast Cancer Stage III, HR+ Breast Cancer
Conditions
Brief summary
Phase III, single-center, randomized, double-blind, placebo-controlled, 2x2 cross- over study, assessing the efficacy of CBD in patients with early HR+ BC, presenting aromatase inhibitor-related musculoskeletal pain
Interventions
DRUGCBD oil
Patients will receive CBD-oral solution 2.5 mg/kg PO BID for a total of 12 weeks.
DRUGPlacebo
Patients will receive placebo for a total of 12 weeks.
Sponsors
Gustave Roussy, Cancer Campus, Grand Paris
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
General inclusion criteria: 1. Patient 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. 2. Patient must be affiliated to a social security system or beneficiary of the same. 3. Patient is ≥ 18 years-old at the time of study inclusion 4. Patient has histologically confirmed invasive Stage I, II, III breast cancer. 5. Patient has breast cancer that is positive for ER and/or PgR (nuclear staining of any intensity ≥ 10%) 6. Patients 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; premenopausal patients are eligible if they are receiving AIs and ovarian function suppression (LHRH agonist). 7. If indicated, patient has completed adjuvant and/or neoadjuvant chemotherapy according to the institutional guidelines, prior to randomization. 8. If indicated, patient has completed adjuvant radiotherapy according to the institutional guidelines, prior to randomization. 9. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 10. Patients should report an Interference pain score of ≥ 4 out of 10 on the Brief Pain Inventory (BPI, Appendix 2) within 7 days before registration. 11. Patient must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other trial procedures. 12. Women 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 14 days of randomization. 13. Women 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: 1. Total 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; 2. Female 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; 3. Placement of an intrauterine device (IUD). Notes: * Use 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. * Women 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. Specific inclusion criteria for CBD use: 14. Patient has adequate bone marrow and organ function as defined by the following local laboratory values: 1. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L 2. Platelets ≥ 100 × 109/L 3. Hemoglobin ≥ 9.0 g/dL 4. Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min by a Cockcroft-Gault formula. 5. Alanine transaminase (ALT) ≤ 1.5 × Upper Limit Normal (ULN) 6. Aspartate transaminase (AST) ≤ 1.5 × ULN 7. Total serum bilirubin ≤ ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin ≤ 1.5 × ULN in patients with well documented Gilbert's Syndrome 8. International 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). 9. Patient 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: * Sodium * Potassium * Phosphorus * Magnesium * Total Calcium 15. Standard 12-lead ECG values defined as the mean of the triplicate ECGs as locally assessed: 1. QTcF interval (using Fridericia's correction) at screening \< 450 msec 2. Mean resting heart rate 50-90 bpm (determined from the ECG)
Exclusion criteria
General
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brief Pain Inventory - Short Form (BPI-SF) Interference score. | Baseline, 4 weeks, 12 weeks, 13 weeks, 17 weeks, 25 weeks, 37 weeks after starting treatment. | The BPI is a 14-item questionnaire that asks patients to rate pain over the last 24 hours and the degree to which it interfered with activities on a 0-10 scale, where higher scores indicate more pain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| EORTC QLQ-C30 | Baseline, 4 weeks, 12 weeks, 13 weeks, 17 weeks, 25 weeks, 37 weeks after starting treatment. | The EORTC Quality of Life Questionnaire-C30 (EORTC QLQ-C30) contains 30 questions and assesses the quality of life of oncological patients multidimensionally over 10 subscales. All sub-scales and the 6 individual items have a score range from 0 to 100 points. A higher score represents better function and a higher quality of life. In the symptom subscale, however, a higher score represents a higher level of symptoms or problems. |
| EORTC QLQ-BR45. | Baseline, 4 weeks, 12 weeks, 13 weeks, 17 weeks, 25 weeks, 37 weeks after starting treatment. | The QLQ-BR45 is a supplementary questionnaire module to be employed in conjunction with the QLQ-C30. The QLQ-BR45 incorporates nine multi-item scales to assess body image, sexual functioning, breast satisfaction, systemic therapy side effects, arm symptoms, breast symptoms, endocrine therapy symptoms, skin mucosis symptoms, endocrine sexual symptoms. In addition, single items assess sexual enjoyment, future perspective and being upset by hair loss. All of the scales and single item measures range in score from 0 to 100. A high score for the functional scales and functional single items represents a high/healthy level of functioning, whereas a high score for the symptom scales and symptom item represents a high level of symptomatology or problems. |
| EORTC QLQ-FA12. | Baseline, 4 weeks, 12 weeks, 13 weeks, 17 weeks, 25 weeks, 37 weeks after starting treatment. | The FA12 is the new fatigue module designed to complement the EORTC QLQ-C30. It consists of 12 items, with four response categories for each item, coded with values from 1 to 4. In accordance with the scales of the EORTC QLQ-C30, the FA12 scores are transformed to the range 0-100, with higher levels indicating greater degrees of fatigue. |
| Hospital Anxiety and Depression Scale (HADS). | Baseline, 4 weeks, 12 weeks, 13 weeks, 17 weeks, 25 weeks, 37 weeks after starting treatment. | HADS is a fourteen-item scale with seven items each for anxiety and depression subscales. Scoring for each item ranges from zero to three. A subscale score \>8 denotes anxiety or depression. |
| Western Ontario and McMaster Universities Osteoarthritis scale (WOMAC). | Baseline, 4 weeks, 12 weeks, 13 weeks, 17 weeks, 25 weeks, 37 weeks after starting treatment. | This is a 24-item questionnaire that is used to assess pain, stiffness, and functioning in the knees and hips during the past week. The test questions are scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). The scores for each subscale are summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. Usually a sum of the scores for all three subscales gives a total WOMAC score, however there are other methods that have been used to combine scores.\[1\] Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. |
| Adherence | Baseline, 4 weeks, 12 weeks, 13 weeks, 17 weeks, 25 weeks, 37 weeks after starting treatment. | Patient's self-reporting through the questionnaire MIS |
| Domain-Specific Risk-Taking (DOSPERT) scale. | Baseline. | The DOSPERT is a risk-taking scale of the 30-item evaluates behavioral intentions, that is, the likelihood with which respondents might engage in risky behaviors originating from five domains of life (ethical, financial, health/safety, social, and recreational risks) using a 7-point rating scale ranging from 1 (Extremely Unlikely) to 7 (Extremely Likely). Higher scores suggesting perceptions of greater risk in the domain of the subscale. |
| Number of side effects measured by CTCAE V.5. | Baseline, 4 weeks, 12 weeks, 13 weeks, 17 weeks, 25 weeks, 37 weeks after starting treatment. | 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, diarrhea or constipation, cognitive dysfunction, nervous system and psychiatric side effects, drug consumption and hospitalizations associated with nervous system and psychiatric disorders. |
| Cannabis Abuse Screening Test (CAST). | Baseline, 4 weeks, 12 weeks, 13 weeks, 17 weeks, 25 weeks, 37 weeks after starting treatment. | The CAST scale is a 6-item scale evaluating cannabis abuse among adolescents and young adults in general population surveys designed at the French Monitoring Center for Drug and Drug addictions (OFDT). A score of less than 3 indicates no addiction risk. A score of 3 or less than 7 indicates low addiction risk, and a score of 7 or above indicates high addiction risk. |
| Medication intake survey (MIS). | Baseline, 4 weeks, 12 weeks, 13 weeks, 17 weeks, 25 weeks, 37 weeks after starting treatment. | A 10-item survey, representing a French validated self-report instrument measuring key adherence properties. Taking adherence is computed over 1 week, 4 weeks and 4 months. A high score represents a high level of adherence |
Countries
France
Contacts
Primary ContactBarbara PISTILLI, MD
Outcome results
None listed