Condition category
Cancer
Date applied
20/05/2005
Date assigned
13/07/2005
Last edited
23/02/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Stopped
Recruitment status
Stopped

Contact information

Type

Scientific

Primary contact

Prof Robert E Coleman

ORCID ID

http://orcid.org/0000-0002-4275-1043

Contact details

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

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT00458796

Protocol/serial number

BISMARK 2005

Study information

Scientific title

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

Acronym

BISMARK

Study hypothesis

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

Not provided at time of registration.

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

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 names

Zoledronic acid

Primary outcome measures

Frequency and timing of all skeletal related events (SREs), defined as fractures, radiotherapy to bone, hypercalcaemia of malignancy, orthopaedic surgery and spinal cord compression.

Secondary outcome measures

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

Overall trial start date

01/09/2005

Overall trial end date

30/09/2013

Reason abandoned

Participant recruitment issue

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

1400

Participant 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)

Recruitment start date

01/09/2005

Recruitment end date

30/09/2013

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Weston Park Hospital
Sheffield
S10 2SJ
United Kingdom

Trial participating centre

Clinical Trials Research Unit
University of Leeds
Leeds
LS2 9JT
United Kingdom

Trial participating centre

St Lukes Cancer Centre at the Royal Surrey
Guildford
GU2 7XX
United Kingdom

Trial participating centre

Shrewsbury and Telford Hospital NHS Trust
Shrewsbury
SY3 8XQ
United Kingdom

Trial participating centre

Western General Hospital
Edinburgh
EH4 2XU
United Kingdom

Trial participating centre

Cancer Research UK Oncology Unit
Southampton General Hospital
Southampton
SO16 6YD
United Kingdom

Sponsor information

Organisation

University of Sheffield (UK)

Sponsor details

Academic Division Research Office
85 Wilkinson Street
Sheffield
S10 2GJ
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Other

Funder name

Clinical Trials Advisory and Awards Committee (CTAAC)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Final publication in preparation

Intention to publish date

Participant level data

Available on request

Results - basic reporting

Publication summary

2012 results in: http://meetinglibrary.asco.org/content/99595-114

Publication citations

  1. Results

    RE Coleman, J Wright, S Houston, R Agrawal, O Pra-Kash Purohit, L Hayward, P Simmonds, A Waterhouse, H Marshall, BISMARK Investigators, Randomized trial of marker-directed versus standard schedule zoledronic acid for bone metastases from breast cancer, J Clin Oncol, 2012 , 30, (suppl; abstr 511).

Additional files

Editorial Notes

23/02/2016: Trial closed prematurely in October 2009 due to poor accrual - 289/1400 patients. Follow-up completed. Not yet published in full.