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 |
| EudraCT/CTIS number | 2005-001376-12 |
| ClinicalTrials.gov number | NCT00458796 |
| Secondary identifying numbers | BISMARK 2005 |
- 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
Contact information
Prof Robert E Coleman
Scientific
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
| Study design | Randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Not specified |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Zoledronic acid |
| Primary outcome measure | 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 study start date | 01/09/2005 |
| 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 | Both |
| Target number of participants | 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
- England
- Scotland
- United Kingdom
Study participating centres
Weston Park Hospital
Sheffield
S10 2SJ
United Kingdom
S10 2SJ
United Kingdom
Clinical Trials Research Unit
University of Leeds
Leeds
LS2 9JT
United Kingdom
Leeds
LS2 9JT
United Kingdom
St Lukes Cancer Centre at the Royal Surrey
Guildford
GU2 7XX
United Kingdom
GU2 7XX
United Kingdom
Shrewsbury and Telford Hospital NHS Trust
Shrewsbury
SY3 8XQ
United Kingdom
SY3 8XQ
United Kingdom
Western General Hospital
Edinburgh
EH4 2XU
United Kingdom
EH4 2XU
United Kingdom
Cancer Research UK Oncology Unit
Southampton General Hospital
Southampton
SO16 6YD
United Kingdom
Southampton
SO16 6YD
United Kingdom
Sponsor information
University of Sheffield (UK)
University/education
University/education
Academic Division Research Office
85 Wilkinson Street
Sheffield
S10 2GJ
England
United Kingdom
"ROR" |
https://ror.org/05krs5044 |
|---|
Funders
Funder type
Other
Clinical Trials Advisory and Awards Committee (CTAAC)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Final publication in preparation |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Plain English results | No | Yes | |||
| Abstract results | results | 20/05/2012 | No | No |
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.
