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
EudraCT/CTIS number 2015-005713-67
IRAS number 197918
Secondary identifying numbers CPMS 34845
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
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-of-zoledronic-acid-for-early-breast-cancer-zolmeno-study

Contact information

Dr Erica Wallis
Public

Sheffield Teaching Hospital NHS Foundation Trust
D Floor, Royal Hallamshire Hospital
Glossop Road
Sheffield
S10 2JF
United Kingdom

Study information

Study designRandomized; Both; Design type: Treatment, Drug, Validation of outcome measures
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details to request a patient information sheet Contact: Erica Wallis, Erica.wallis@sth.nhs.uk
Scientific titleThe 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 acronymZOLMENO
Study objectivesThe 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) studiedBreast Cancer
InterventionParticipants 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 typeOther
Primary outcome measureChange in serum follistatin measured by ELISA using validated lab kits at day 28 post-ZOL administration.
Secondary outcome measuresThe 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:
1. Change in serum follistatin measured by ELISA using validated lab kits at day 7 and 28 post-ZOL infusion
2. Change in serum activin measured by ELISA using validated lab kits at day 7 and day 28 post-ZOL infusion
3. Change in serum follistatin measured by ELISA using validated lab kits from day 0 (surgery) to day 21 and day 28 post-surgery
4. Change in serum activin measured by ELISA using validated lab kits from day 0 (surgery) to day 21 and day 28 post-surgery
5. Follistatin and activin levels measured by ELISA using validated lab kits in tumour samples obtained at surgery
Overall study start date21/09/2015
Completion date10/12/2024

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit40 Years
SexFemale
Target number of participantsPlanned Sample Size: 80; UK Sample Size: 80
Total final enrolment19
Key inclusion criteria1. 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 criteria1. 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 enrolment01/11/2017
Date of final enrolment31/12/2022

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

Weston Park Hospital Cancer Clinical Trials Centre
Sheffield Teaching Hospitals NHS Foundation Trust
Whitham Road
Sheffield
S10 2SJ
United Kingdom

Sponsor information

Sheffield Teaching Hospitals NHS Foundation Trust
Hospital/treatment centre

Clinical Research & Innovation Office
D Floor, Royal Hallamshire Hospital
Glossop Road
Sheffield
S10 2JF
England
United Kingdom

ROR logo "ROR" https://ror.org/018hjpz25

Funders

Funder type

Government

Yorkshire Cancer Research
Government organisation / Trusts, charities, foundations (both public and private)
Alternative name(s)
YCR
Location
United Kingdom

Results and Publications

Intention to publish date31/12/2024
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryData sharing statement to be made available at a later date
Publication and dissemination planThe trial results are planned to be published in a high-impact peer reviewed scientific journal and by scientific conference presentation. Additional documents are available upon request from Erica Wallis (erica.wallis@sth.nhs.uk).
IPD sharing planThe 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

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.