Additional identifiers
EudraCT number
2015-005713-67
ClinicalTrials.gov number
Protocol/serial number
34845
Study information
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
Acronym
The ZOLMENO study
Study hypothesis
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
Yorkshire & The Humber - Leeds East Research Ethics Committee, 09/06/2016, ref: 16/YH/0151
Study design
Randomised; Both; Design type: Treatment, Drug, Validation of outcome measures
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet Contact: Erica Wallis, Erica.wallis@sth.nhs.uk
Condition
Specialty: Cancer, Primary sub-specialty: Breast Cancer; UKCRC code/ Disease: Cancer/ Malignant neoplasm of breast
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
Phase
Phase II
Drug names
Primary outcome measure
Change in serum follistatin measured by ELISA using validated lab kits at day 28 post-ZOL administration.
Secondary outcome measures
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:
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 trial start date
21/09/2015
Overall trial end date
31/12/2021
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Female patients aged ≥ 40
2. Histologically confirmed early breast cancer
3. Tumour size more than 1cm (≥ 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
Participant type
Patient
Age group
Adult
Gender
Female
Target number of participants
Planned Sample Size: 80; UK Sample Size: 80
Participant 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
Recruitment start date
01/11/2017
Recruitment end date
31/12/2019
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Weston Park Hospital Cancer Clinical Trials Centre
Sheffield Teaching Hospitals NHS Foundation Trust
Whitham Road
Sheffield
S10 2SJ
United Kingdom
Funders
Funder type
Government
Funder name
Yorkshire Cancer Research
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
Results and Publications
Publication and dissemination plan
The 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 statement:
The data sharing plans for the current study are unknown and will be made available at a later date
Intention to publish date
31/12/2022
Participant level data
To be made available at a later date
Basic results (scientific)
Publication list