Does zoledronic acid alter levels of reproductive hormones and how does this affect the tumour and bone in pre- and post-menopausal women with early breast cancer?
| ISRCTN | ISRCTN15749696 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN15749696 |
| Clinical Trials Information System (CTIS) | 2015-005713-67 |
| Integrated Research Application System (IRAS) | 197918 |
| Protocol serial number | CPMS 34845 |
| Sponsor | Sheffield Teaching Hospitals NHS Foundation Trust |
| Funder | Yorkshire Cancer Research |
- Submission date
- 04/09/2017
- Registration date
- 03/10/2017
- Last edited
- 30/01/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Plain English summary of protocol
Contact information
Public
Sheffield Teaching Hospital NHS Foundation Trust
D Floor, Royal Hallamshire Hospital
Glossop Road
Sheffield
S10 2JF
United Kingdom
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Randomized; Both; Design type: Treatment, Drug, Validation of outcome measures |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| Scientific title | The role of ZOLedronic acid and MENOpausal status on the tumour and bone microenvironment in patients with early breast cancer: a single centre, randomised, proof of concept clinical study |
| Study acronym | ZOLMENO |
| Study objectives | The aim of this study is to identify the mechanisms responsible for the differential effect of zoledronic acid seen in pre- and post-menopausal women with early breast cancer. This study has arisen directly from the AZURE trial which was the first to demonstrate that menopausal status is a significant modifier of the effects of zoledronic acid (ZOL) in early breast cancer in that women who were post-menopausal significantly benefitted from adjuvant ZOL (with prevention of one death in every six), whereas this effect was not seen in pre-menopausal women. It is hypothesised that this differential effect may be linked to differential levels of follistatin and activin in pre- and post-menopausal women. |
| Ethics approval(s) | Yorkshire & The Humber - Leeds East Research Ethics Committee, 09/06/2016, ref: 16/YH/0151 |
| Health condition(s) or problem(s) studied | Breast Cancer |
| Intervention | Participants in both arms receive a single intravenous infusion of zoledronic acid 4mg in 100ml 0.9% sodium chloride over 15 minutes on either day seven pre-surgery or day 21 post-surgery. The purpose of the randomisation is to allow the effect of zoledronic acid to be separated from the effect of surgery and to permit both pre-administration and post administration bone marrow biopsies to be collected whilst the participants are under anaesthetic during surgery. Participants are randomised by the Informatics Team at the Cancer Clinical Trials Office at Weston Park Hospital using a computer generated randomisation schedule which includes age group stratification: 40-54 years and ≥55 years. |
| Intervention type | Other |
| Primary outcome measure(s) |
Change in serum follistatin measured by ELISA using validated lab kits at day 28 post-ZOL administration. |
| Key secondary outcome measure(s) |
The following secondary outcome measures, all compared relative to menopausal status (pre- vs. post-menopausal) and timing of ZOL administration (Group A vs. Group B), includes: |
| Completion date | 10/12/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 40 Years |
| Sex | Female |
| Target sample size at registration | 80 |
| Total final enrolment | 19 |
| Key inclusion criteria | 1. Female patients aged ≥40 years 2. Histologically confirmed early breast cancer 3. Tumour size more than 1 cm (≥ T1) 4. Any nodal status including unknown (≥N0) 5. Scheduled for surgery as primary treatment 6. Any tumour hormone receptor (ER/PR) or HER2 status 7. ECOG performance status of 0, 1 or 2 (appendix 2) 8. Menopausal status defined clinically by menstrual and clinical history, or where this is indeterminate patient is willing to have biochemical profile testing following consent 9. Measured or calculated Glomerular Filtration Rate (GFR) ≥30 ml/min (Cockcroft and Gault formula, appendix 3) 10. Serum corrected calcium ≥2.2mmol/L 11. APTT 30.5 seconds 12. PT 13.2 seconds or INR <1.5 13. Platelets 100 x 109/L 14. Or clotting abnormalities which are due to be reversed as part of standard care by the time of bone marrow sampling (e.g. stopping anticoagulants prior to surgery) 15. Potentially fertile women must have a negative pregnancy test within 72 hours prior to randomisation, and not be breast-feeding 16. Potentially fertile women must agree to use effective, medically approved, barrier contraception from the time of consent to 30 days after their zoledronic acid infusion 17. Potential participants must be willing to have the required mandatory samples taken, including bone marrow aspiration and trephine at the time of surgery 18. Potential participants must have the mental capacity to understand the study information, make an informed choice regarding participation and to provide written informed consent |
| Key exclusion criteria | 1. Any previous diagnosis or treatment of cancer that could confound results and endpoints (allowed situations include non-melanomatous skin cancer or superficial bladder cancer) 2. Patients with an estimated life expectancy of <6 months 3. Any diagnosis of a bone marrow disorder 4. Any previous bisphosphonate treatment 5. Use of hormone replacement therapy (HRT) in the past 30 days or a diagnosis of hormonal imbalance such as polycystic ovarian syndrome 6. Current active dental problems including dental abscess or infection of the jawbone (maxilla or mandible), any open oral wounds or a current or previous diagnosis of osteonecrosis of the jaw 7. Recent (within 4 weeks) or planned dental or jaw surgery (recent dental fillings, scaling, polishing or minor gingival surgery do not exclude the patient) 8. Any other serious medical or psychiatric condition which in the opinion of the investigator could affect participation in the ZOLMENO study, including dehydration, notable electrolyte disturbances, significant use of nephrotoxic, antiangiogenic or hypocalcaemia inducing drugs or history of significant renal failure, which in the opinion of the screening investigator, would render the patient unsuitable for zoledronic acid or sample collection |
| Date of first enrolment | 01/11/2017 |
| Date of final enrolment | 31/12/2022 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centre
Whitham Road
Sheffield
S10 2SJ
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No | ||
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
30/01/2025: The following changes were made to the study record:
1. IRAS number added.
2. The overall study end date was changed from 31/12/2023 to 10/12/2024.
05/04/2023: The following changes were made to the trial record:
1. Total final enrolment added.
2. The recruitment end date was changed from 30/04/2023 to 31/12/2022.
31/01/2022: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/12/2019 to 30/04/2023.
2. The overall end date was changed from 31/12/2021 to 31/12/2023.
3. The intention to publish date was changed from 31/12/2022 to 31/12/2024.
4. A contact email was updated.
5. The sponsor address was updated.
24/05/2019: Cancer Research UK lay summary link added to plain English summary field.
05/04/2019: Internal review.
03/04/2019: The condition has been changed from "Specialty: Cancer, Primary sub-specialty: Breast Cancer; UKCRC code/ Disease: Cancer/ Malignant neoplasm of breast" to "Breast Cancer" following a request from the NIHR.
05/03/2019: Internal review.
06/06/2018: Internal review
14/05/2018: Internal review.
16/01/2018: Internal review.
