Comparison of Two Schedules of Zoledronic Acid in Treating Patients With Breast Cancer That Has Spread to the Bone

May 23, 2022 updated by: University of Leeds

Cost-Effective Use of Bisphosphonates in Metastatic Bone Disease - A Comparison of Bone Marker Directed Zoledronic Acid Therapy to a Standard Schedule

RATIONALE: Zoledronic acid may help decrease the risk of broken bones, bone pain, and other symptoms caused by bone metastases. It may also help patients live more comfortably.

PURPOSE: This randomized clinical trial is studying different schedules of zoledronic acid to compare how well they work in treating patients with breast cancer that has spread to the bone.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

Compare the frequency and timing of serious related events (e.g., fractures, radiotherapy to bone, hypercalcemia of malignancy, orthopedic surgery, and spinal cord compression) in patients with advanced breast cancer metastatic to the bone treated with bone marker-directed schedule vs standard schedule zoledronic acid.

Secondary

Compare the quality of life of patients treated with these regimens.
Compare the clinical burden of skeletal complications in these patients.
Compare pain, performance status, and analgesic use (PPA score) in these patients.
Compare the incidence of new bone metastases in these patients.
Compare overall survival of these patients.
Compare bisphosphonate use and expenditure on administration in these patients.

OUTLINE: This is an open-label, randomized, controlled, parallel-group, multicenter study. Patients are stratified according to treatment center, gender, type of concurrent systemic therapy at study entry (endocrine therapy [with or without trastuzumab (Herceptin^®)] vs chemotherapy [with or without trastuzumab] vs trastuzumab alone vs chemotherapy and endocrine therapy [with or without trastuzumab] vs no systemic anticancer treatment), prior skeletal-related event (yes vs no), duration of bisphosphonate use for metastatic disease prior to study entry (4-6 months vs 6-12 months), type of metastases present at study entry (bone only vs bone and soft tissue vs bone and visceral metastases vs bone, soft tissue, and visceral metastases). Patients are randomized to 1 of 2 treatment arms.

Arm I (standard schedule): Patients receive zoledronic acid IV over 15 minutes once every 3-4 weeks for 24 months.
Arm II (bone marker-directed schedule): Patients receive zoledronic acid IV over 15 minutes once every 3-4, 8-9, or 15-16 weeks (based on serum N-telopeptide:creatinine ratio) for 24 months.

Quality of life is assessed at baseline and at 3, 6, 9, 12, 18, and 24 months.

After completion of study therapy, patients are followed periodically for up to 3 years.

PROJECTED ACCRUAL: A total of 1,500 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Anticipated)

1500

Phase

Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United Kingdom
- England
  - Bournemouth, England, United Kingdom, BH7 7DW
    - Royal Bournemouth Hospital
  - Derby, England, United Kingdom, DE1 2QY
    - Derbyshire Royal Infirmary
  - Doncaster, England, United Kingdom, DN2 5LT
    - Doncaster Royal Infirmary
  - Durham, England, United Kingdom, DH1 5TW
    - University Hospital of North Durham
  - Grimsby, England, United Kingdom, DN33 2BA
    - Diana Princess of Wales Hospital
  - Guildford, England, United Kingdom, GU2 7XX
    - St. Luke's Cancer Centre at Royal Surrey County Hospital
  - Huddersfield, West Yorks, England, United Kingdom, HD3 3EA
    - Huddersfield Royal Infirmary
  - Liverpool, England, United Kingdom, L7 8XP
    - Royal Liverpool University Hospital
  - London, England, United Kingdom, EC1A 7BE
    - Saint Bartholomew's Hospital
  - Manchester, England, United Kingdom, M20 4BX
    - Christie Hospital
  - Manchester, England, United Kingdom, M20 8LR
    - Withington Hospital
  - Merseyside, England, United Kingdom, CH63 4JY
    - Clatterbridge Centre for Oncology
  - Nuneaton, England, United Kingdom, CV10 7DJ
    - George Eliot Hospital
  - Poole Dorset, England, United Kingdom, BH15 2JB
    - Dorset Cancer Centre
  - Scunthorpe, England, United Kingdom, DN15 7BH
    - Scunthorpe General Hospital
  - Sheffield, England, United Kingdom, S1O 2SJ
    - Cancer Research Centre at Weston Park Hospital
  - Shrewsbury, England, United Kingdom, SY3 8XQ
    - Royal Shrewsbury Hospital
  - Solihull, England, United Kingdom, B91 2JL
    - Solihull Hospital
  - Southampton, England, United Kingdom, SO16 6YD
    - Southampton General Hospital
  - Warwick, Warwickshire, England, United Kingdom, CV34 5BJ
    - South Warwickshire Hospital
  - Westcliff-On-Sea, England, United Kingdom, SS0 0RY
    - Southend University Hospital NHS Foundation Trust
  - Winchester, England, United Kingdom, SO22 5DG
    - Royal Hampshire County Hospital
- Scotland
  - Glasgow, Scotland, United Kingdom, G12 0YN
    - Beatson West of Scotland Cancer Centre
  - Glasgow, Scotland, United Kingdom, G11 6NT
    - Western Infirmary
  - Glasgow, Scotland, United Kingdom, G12 0YN
    - Hairmyres Hospital
  - Kilmarnock, Scotland, United Kingdom, KA2 OBE
    - Crosshouse Hospital
- Wales
  - Cardiff, Wales, United Kingdom, CF14 2TL
    - Velindre Cancer Center at Velindre Hospital
  - Haverfordwest, Wales, United Kingdom, SA61 2PZ
    - Withybush General Hospital
  - Newport Gwent, Wales, United Kingdom, NP9 2UB
    - Royal Gwent Hospital
  - Swansea, Wales, United Kingdom, SA2 8QA
    - South West Wales Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

Histologically confirmed primary breast cancer
- Advanced disease
Radiographic confirmation of bone metastases (≥ 1 bone scan lesion must be confirmed as metastatic by plain radiographs or CT scan/MRI)
- Must have received zoledronic acid to treat metastatic bone disease (i.e., ≥ 4 or 5 zoledronic acid treatments prior to study entry for patients receiving 4- or 3-weekly infusions, respectively) for ≥ 4 months prior to study entry
- Any bisphosphonate to treat metastatic bone disease allowed provided it was not given for more than 12 months prior to study entry
No metabolic bone disease (e.g., Paget's disease of bone)
- Osteoporosis allowed
No brain metastases
Hormone receptor status not specified

PATIENT CHARACTERISTICS:

Male or female
Menopausal status not specified
WHO or ECOG performance status 0-2
Life expectancy ≥ 6 months
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
AST and ALT ≤ 3 times upper limit of normal (ULN)
Bilirubin ≤ 1.5 times ULN
Creatinine clearance ≥ 30 mL/min
No poor venous access
No concurrent active dental problems, including infection of the teeth or jawbone (maxilla or mandibular)
No prior or current diagnosis of osteonecrosis of the jaw
No other cancer within the past 5 years except nonmelanomatous skin cancer, carcinoma in situ of the uterine cervix, or superficial bladder cancer treated with curative intent

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No other prior bisphosphonate treatment within the past 3 weeks
No treatment with systemic bone-seeking radioisotopes (e.g., strontium chloride Sr 89, samarium Sm 153 lexidronam pentasodium) within the past 3 months
No wide-field (hemibody) radiotherapy within the past 3 months
- Recent standard-field, localized radiotherapy allowed
No dental or jaw surgery (e.g., extractions, implants) within the past 4 weeks
No other concurrent bisphosphonates
No concurrent medication with drugs known to affect bone metabolism (e.g., calcitonin or high-dose systemic corticosteroids [> 10 mg prednisolone/day or equivalent])
- Systemic or oral corticosteroids allowed for clearly indicated conditions (e.g., chemotherapy-induced emesis, brain metastases, compression syndromes)
Concurrent chemotherapy, biological therapy, or endocrine therapy allowed

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Fractures
Radiotherapy to bone either for relief of pain or to treat or prevent pathological fractures or spinal cord compression
Hypercalcemia of malignancy
Orthopedic surgery to prevent or treat pathological fractures or spinal cord compression
Spinal cord compression

Secondary Outcome Measures

Outcome Measure
Overall survival
Quality of life as measured by QLQ-C30 and the QLQ-BR23 breast-specific module
Clinical burden of skeletal complications
Pain, performance status, and analgesic use
Incidence of new bone metastases
Bisphosphonate use and expenditure on administration
Health care utilization
Clinical utility of the "point of care" test for N-telopeptides (NTx) excretion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Leeds

Collaborators

University of Sheffield

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2006

Study Registration Dates

First Submitted

April 9, 2007

First Submitted That Met QC Criteria

April 9, 2007

First Posted (Estimate)

April 11, 2007

Study Record Updates

Last Update Posted (Actual)

May 27, 2022

Last Update Submitted That Met QC Criteria

May 23, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

CDR0000538879
NCRI-BISMARK
ISRCTN83586728
EU-20716
EUDRACT-2005-001376-12

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.