Hormone receptor positive breast cancer recurrence Cancer Breast cancer
Conditions
Interventions
Metformin and zoledronic acid will be evaluated when combined with an aromatase inhibitor (anastrozole, letrozole or examestane) in a 2x2x2 factorial design.
Sponsors
Queen Mary University of London
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 30/03/2017: 1. Informed Consent 2. = 75 years 3. Post-menopausal women confirmed by previous AI use only 4. Previous ER+ breast cancer treated by endocrine therapy. ER+ is equivalent to an Allred/Quick score of 3 or above. Additional treatment with trastuzumab (if Her2+) and chemotherapy are allowed. 5. Surgery for breast cancer plus 5 years adjuvant endocrine therapy (at least 4 years with AI completed within the last 6 years; therefore 5-11 years from diagnosis) 6. Breast cancer must have been node positive AND/OR =2cm in size (measurement based on invasive tumour) 7. A bilateral mammogram (unless unilateral mastectomy in which case unilateral mammogram) must have been taken within the last year and not show any evidence of breast cancer. Women who have had a bilateral mastectomy, where contralateral mastectomy was either prophylactic or was performed to treat breast cancers diagnosed at the same time, are eligible and a mammogram is not required in this case. 8. A baseline bone mineral density (BMD) scan within the last year; DXA must include hip (femoral neck or proximal femur) AND lumbar spine and can include forearm. 9. Low BMD (where T-score is -4.0 =T= -2.0) women are eligible for metformin and aromatase inhibitor treatments. This must be managed in accordance with local clinical procedures for treatment of osteoporosis i.e., take bisphosphonate treatment and have regular DXA scans Previous inclusion criteria: 1. Informed consent 2. = 75 years old 3. Post-menopausal women (defined as at least 12 months since last period) 4. Previous ER+ (or PR+) breast cancer treated by endocrine therapy. ER+ is equivalent to an Allred/Quick score of 3 or above. Additional trastuzumab (if Her2+) and chemotherapy are allowed. 5. Surgery for breast cancer plus 4-6 years adjuvant endocrine therapy (at least 4 years with AI completed within the last 3 years; therefore maximum of 9 years from diagnosis) 6. Breast cancer must have been node positive (macrometastases) AND/OR =2cm 7. A bilateral mammogram (unless unilateral mastectomy in which case unilateral mammogram) must have been taken within the last year and not show any evidence of breast cancer. Women who have had a bilateral mastectomy are eligible and a mammogram is not required in this case. 8. A baseline bone mineral density scan within the last year; DXA must include hip (femoral neck or proximal femur) AND lumbar spine and can include forearm. 9. Low BMD (where T-score is -4.0 =T= -2.0) and no more than one known low trauma vertebral fracture AND/OR high FRAX score (http://www.shef.ac.uk/FRAX/tool.aspx) are eligible for metformin and aromatase inhibitor treatments. This must be managed in accordance with local clinical procedures for treatment of osteoporosis i.e., take bisphosphonate treatment and have regular DXA scans.
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 30/03/2017: 1. Any recurrence or clinical suspicion of active breast cancer (including DCIS) 2. Any other previous cancer (apart from original breast cancer) (except non-melanoma skin cancer or in situ cancer of the cervix). 3. Current (or intended) use of oestrogen-based hormone replacement therapy (HRT) 4. Type I diabetes 5. Type II diabetes AND osteoporosis 6. T-scores of less than minus four, or two or more known low trauma vertebral fractures 7. Abnormal renal function as classified as eGFR 7.0 mmol/L) but must be on antidiabetic medication 14. Known hypersensitivity or intolerance to metformin 15. Currently taking meglitinides, sulfonylureas, thiazolidinediones (glitazones) or insulin 16. History of acidosis of any type 17. Habitual intake of 3 or more units of alcohol per day Excluded from zoledronic randomisation only 18. Low BMD (where T-score is -4.0 =T= -2.0). This must be managed in accordance with local clinical procedures for treatment of osteoporosis i.e., take bisphosphonate treatment and have regular DXA scans. See Appendix 4 for definitions. Excluded from AI randomisation only 19. Currently being treated by extended AI 20. Current use (or intention to use) raloxifene, tamoxifen or any other SERM Previous exclusion criteria: 1. Any recurrence or clinical suspicion of active breast cancer (including DCIS) 2. Any other previous cancer (apart from original breast cancer) in the past 5 years (except non-melanoma skin cancer or in situ cancer of the cervix) 3. Current treatment (or intended use) of oestrogen-based hormone replacement therapy (HRT) 4. Type I diabetes 5. Diabetes (Types I and II) AND osteoporosis 6. T-scores of less than minus four, or two or more known low trauma vertebral fractures 7. Abnormal renal function as classified as eGFR < 40ml/min. If possible the CKD-EP1 equation should be used to calculate eGFR but the Cockroft-Gault formula is acceptable 8. Any severe concomitant disease, e.g. congestive cardiac failure, that would, at the discre
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary objective is to determine acceptability and feasibility of recruitment, recruitment rate and number of sites required for main trial. Primary endpoint is the recruitment of 100 patients within 12 months. Assessment method is recruitment numbers via randomisation figures and screening logs. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary objectives are: 1. To determine reasons for non-participation/drop-outs and address these for main trial (endpoint: recruitment and follow-up of 100 patients; assessment method: analysis of screening logs to understand reasons for non-participation) 2. To evaluate treatment adherence and reasons for stopping (endpoint: 6 monthly follow-up; assessment method: data collected on CRFs, PROs [FACT-ES, EQ5DL], Kaplan Meier curves) 3. To determine reasons for non-adherence and address for main trial (endpoint: 6 monthly follow-up; assessment method: data collected on CRFs, PROs [FACT-ES, EQ5DL]) 4. To assess the use of referral through GP surgeries as PICs local to sites via the PCRN/LCRN (endpoint: the recruitment of 100 patients; assessment method: recruitment method captured by CRF and assessment of referral letters) 5. To investigate feasibility of the use of email for data collection of PROs from patients (enpoint: at baseline + asked again at 12 and 24 months to see if email use increases with time; assessment method: comparison of numbers of patients providing data by email or by post and quality and completeness of that data) 6. To assess acceptability of investigations for main trial (endpoint: at 12 months and ongoing until trial ends; assessment method: number of patients providing blood samples [data on CRF], PRO data [FACT-ES, EQ5DL]) | — |
Countries
United Kingdom
Contacts
Public ContactJack Cuzick
Outcome results
None listed