Cost-effective use of BISphosphonates in metastatic bone disease - a comparison of bone MARKer directed zoledronic acid therapy to a standard schedule

ISRCTN	ISRCTN83586728
DOI	https://doi.org/10.1186/ISRCTN83586728
ClinicalTrials.gov (NCT)	NCT00458796
Clinical Trials Information System (CTIS)	2005-001376-12
Protocol serial number	BISMARK 2005
Sponsor	University of Sheffield (UK)
Funder	Clinical Trials Advisory and Awards Committee (CTAAC)

Submission date: 20/05/2005
Registration date: 13/07/2005
Last edited: 19/03/2020

Recruitment status: Stopped
Overall study status: Stopped
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

http://cancerhelp.cancerresearchuk.org/trials/a-trial-looking-at-zoledronic-acid-for-breast-cancer-that-has-spread-to-the-bones2

Contact information

Prof Robert E Coleman
Scientific

Cancer Research Centre
Academic Unit of Clinical Oncology
Weston Park Hospital
Whitham Road
Sheffield
S10 2SJ
United Kingdom

ORCID ID	0000-0002-4275-1043

Study information

Primary study design	Interventional
Study design	Randomised controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Cost-effective use of BISphosphonates in metastatic bone disease - a comparison of bone MARKer directed zoledronic acid therapy to a standard schedule
Study acronym	BISMARK
Study objectives	It is the aim of this trial to determine whether a bone marker directed schedule of bisphosphonate therapy is comparable with a fixed 3-4 weekly strategy in preventing skeletal related events and maintaining quality of life.
Ethics approval(s)	Not provided at time of registration.
Health condition(s) or problem(s) studied	Advanced breast cancer
Intervention	Standard schedule of zoledronic acid (4-weekly) versus marker-directed schedule of zoledronic acid (4, 8 or 16-weekly - variable - dependent on urinary Ntx/creatinine ratio measured every 4 months)
Intervention type	Drug
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Zoledronic acid
Primary outcome measure(s)	Frequency and timing of all skeletal related events (SREs), defined as fractures, radiotherapy to bone, hypercalcaemia of malignancy, orthopaedic surgery and spinal cord compression.
Key secondary outcome measure(s)	1. Quality of life 2. Clinical burden of skeletal complications 3. Pain, performance status and analgesic use (PPA score) 4. The incidence of new bone metastases 5. Overall survival 6. Bisphosphonate use and expenditure on administration Sub-studies in a sub-set of the study population will compare: 1. Health care utilisation 2. Evaluation of the clinical utility of the 'point of care' test for NTX excretion 3. Changes in serum markers of bone metabolism
Completion date	30/09/2013
Reason abandoned (if study stopped)	Participant recruitment issue

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	1400
Key inclusion criteria	1. Patients with advanced breast cancer with radiographic confirmation of bone metastases 2. Men or women aged ≥18 years 3. World Health Organisation (WHO) (Eastern Cooperative Oncology Group [ECOG]) performance status 0-2 4. Women of child-bearing potential must be using a reliable and appropriate method of contraception 5. Ability to read and complete the European Organisation for Research and Treatment of Cancer (EORTC) and pain quality of life (QoL) questionnaires
Key exclusion criteria	1. Bisphosphonate treatment within the 4 weeks prior to planned first study treatment 2. Abnormal renal function as evidenced by a calculated creatinine clearance <30 ml/minute 3. Poor venous access 4. Metabolic bone disease (e.g. Paget's disease of bone) 5. Unable to comply with study procedures, especially the reliable collection of urine samples for bone resorption marker measurements 6. Estimated life expectancy of <6 months 7. Treatment with systemic bone seeking radioisotopes (e.g. strontium, samarium) within the 3 months prior to study entry 8. Wide field (hemi-body) radiotherapy within the 3 months prior to study entry 9. Concomitant medication with drugs known to affect bone metabolism 10. Pregnancy or breast-feeding 11. Current active dental problems including infection of the teeth or jawbone (maxilla or mandibular), or a current or prior diagnosis of osteonecrosis of the jaw (ONJ) 12. Recent (within 4 weeks of study entry) or planned dental or jaw surgery (e.g. extractions, implants)
Date of first enrolment	01/09/2005
Date of final enrolment	30/09/2013

Locations

Countries of recruitment

United Kingdom
England
Scotland

Study participating centres

Weston Park Hospital

Sheffield
S10 2SJ
United Kingdom

Clinical Trials Research Unit

University of Leeds
Leeds
LS2 9JT
United Kingdom

St Lukes Cancer Centre at the Royal Surrey

Guildford
GU2 7XX
United Kingdom

Shrewsbury and Telford Hospital NHS Trust

Shrewsbury
SY3 8XQ
United Kingdom

Western General Hospital

Edinburgh
EH4 2XU
United Kingdom

Cancer Research UK Oncology Unit

Southampton General Hospital
Southampton
SO16 6YD
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Abstract results	results	20/05/2012		No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Plain English results				No	Yes

Editorial Notes

RP 19/03/2020: EudraCT number added.
26/10/2018: Cancer Research UK lay results summary link added to Results (plain English)
23/02/2016: Trial closed prematurely in October 2009 due to poor accrual - 289/1400 patients. Follow-up completed. Not yet published in full.