search
Back to results

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

Primary Purpose

Breast Cancer, Hypercalcemia of Malignancy, Metastatic Cancer

Status
Terminated
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
zoledronic acid
quality-of-life assessment
Sponsored by
University of Leeds
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Breast Cancer focused on measuring hypercalcemia of malignancy, musculoskeletal complications, pain, stage IV breast cancer, male breast cancer, recurrent breast cancer, bone metastases

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Royal Bournemouth Hospital
  • Derbyshire Royal Infirmary
  • Doncaster Royal Infirmary
  • University Hospital of North Durham
  • Diana Princess of Wales Hospital
  • St. Luke's Cancer Centre at Royal Surrey County Hospital
  • Huddersfield Royal Infirmary
  • Royal Liverpool University Hospital
  • Saint Bartholomew's Hospital
  • Christie Hospital
  • Withington Hospital
  • Clatterbridge Centre for Oncology
  • George Eliot Hospital
  • Dorset Cancer Centre
  • Scunthorpe General Hospital
  • Cancer Research Centre at Weston Park Hospital
  • Royal Shrewsbury Hospital
  • Solihull Hospital
  • Southampton General Hospital
  • South Warwickshire Hospital
  • Southend University Hospital NHS Foundation Trust
  • Royal Hampshire County Hospital
  • Western Infirmary
  • Beatson West of Scotland Cancer Centre
  • Hairmyres Hospital
  • Crosshouse Hospital
  • Velindre Cancer Center at Velindre Hospital
  • Withybush General Hospital
  • Royal Gwent Hospital
  • South West Wales Cancer Institute

Outcomes

Primary Outcome Measures

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

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
Overall survival
Bisphosphonate use and expenditure on administration
Health care utilization
Clinical utility of the "point of care" test for N-telopeptides (NTx) excretion

Full Information

First Posted
April 9, 2007
Last Updated
May 23, 2022
Sponsor
University of Leeds
Collaborators
University of Sheffield
search

1. Study Identification

Unique Protocol Identification Number
NCT00458796
Brief Title
Comparison of Two Schedules of Zoledronic Acid in Treating Patients With Breast Cancer That Has Spread to the Bone
Official Title
Cost-Effective Use of Bisphosphonates in Metastatic Bone Disease - A Comparison of Bone Marker Directed Zoledronic Acid Therapy to a Standard Schedule
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Terminated
Why Stopped
Lower than expected recruitment
Study Start Date
March 2006 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
University of Leeds
Collaborators
University of Sheffield

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, Hypercalcemia of Malignancy, Metastatic Cancer, Musculoskeletal Complications, Pain
Keywords
hypercalcemia of malignancy, musculoskeletal complications, pain, stage IV breast cancer, male breast cancer, recurrent breast cancer, bone metastases

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Not Applicable
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1500 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
zoledronic acid
Intervention Type
Procedure
Intervention Name(s)
quality-of-life assessment
Primary Outcome Measure Information:
Title
Fractures
Title
Radiotherapy to bone either for relief of pain or to treat or prevent pathological fractures or spinal cord compression
Title
Hypercalcemia of malignancy
Title
Orthopedic surgery to prevent or treat pathological fractures or spinal cord compression
Title
Spinal cord compression
Secondary Outcome Measure Information:
Title
Quality of life as measured by QLQ-C30 and the QLQ-BR23 breast-specific module
Title
Clinical burden of skeletal complications
Title
Pain, performance status, and analgesic use
Title
Incidence of new bone metastases
Title
Overall survival
Title
Bisphosphonate use and expenditure on administration
Title
Health care utilization
Title
Clinical utility of the "point of care" test for N-telopeptides (NTx) excretion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert E. Coleman, MD, FRCP
Organizational Affiliation
Cancer Research Centre at Weston Park Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Royal Bournemouth Hospital
City
Bournemouth
State/Province
England
ZIP/Postal Code
BH7 7DW
Country
United Kingdom
Facility Name
Derbyshire Royal Infirmary
City
Derby
State/Province
England
ZIP/Postal Code
DE1 2QY
Country
United Kingdom
Facility Name
Doncaster Royal Infirmary
City
Doncaster
State/Province
England
ZIP/Postal Code
DN2 5LT
Country
United Kingdom
Facility Name
University Hospital of North Durham
City
Durham
State/Province
England
ZIP/Postal Code
DH1 5TW
Country
United Kingdom
Facility Name
Diana Princess of Wales Hospital
City
Grimsby
State/Province
England
ZIP/Postal Code
DN33 2BA
Country
United Kingdom
Facility Name
St. Luke's Cancer Centre at Royal Surrey County Hospital
City
Guildford
State/Province
England
ZIP/Postal Code
GU2 7XX
Country
United Kingdom
Facility Name
Huddersfield Royal Infirmary
City
Huddersfield, West Yorks
State/Province
England
ZIP/Postal Code
HD3 3EA
Country
United Kingdom
Facility Name
Royal Liverpool University Hospital
City
Liverpool
State/Province
England
ZIP/Postal Code
L7 8XP
Country
United Kingdom
Facility Name
Saint Bartholomew's Hospital
City
London
State/Province
England
ZIP/Postal Code
EC1A 7BE
Country
United Kingdom
Facility Name
Christie Hospital
City
Manchester
State/Province
England
ZIP/Postal Code
M20 4BX
Country
United Kingdom
Facility Name
Withington Hospital
City
Manchester
State/Province
England
ZIP/Postal Code
M20 8LR
Country
United Kingdom
Facility Name
Clatterbridge Centre for Oncology
City
Merseyside
State/Province
England
ZIP/Postal Code
CH63 4JY
Country
United Kingdom
Facility Name
George Eliot Hospital
City
Nuneaton
State/Province
England
ZIP/Postal Code
CV10 7DJ
Country
United Kingdom
Facility Name
Dorset Cancer Centre
City
Poole Dorset
State/Province
England
ZIP/Postal Code
BH15 2JB
Country
United Kingdom
Facility Name
Scunthorpe General Hospital
City
Scunthorpe
State/Province
England
ZIP/Postal Code
DN15 7BH
Country
United Kingdom
Facility Name
Cancer Research Centre at Weston Park Hospital
City
Sheffield
State/Province
England
ZIP/Postal Code
S1O 2SJ
Country
United Kingdom
Facility Name
Royal Shrewsbury Hospital
City
Shrewsbury
State/Province
England
ZIP/Postal Code
SY3 8XQ
Country
United Kingdom
Facility Name
Solihull Hospital
City
Solihull
State/Province
England
ZIP/Postal Code
B91 2JL
Country
United Kingdom
Facility Name
Southampton General Hospital
City
Southampton
State/Province
England
ZIP/Postal Code
SO16 6YD
Country
United Kingdom
Facility Name
South Warwickshire Hospital
City
Warwick, Warwickshire
State/Province
England
ZIP/Postal Code
CV34 5BJ
Country
United Kingdom
Facility Name
Southend University Hospital NHS Foundation Trust
City
Westcliff-On-Sea
State/Province
England
ZIP/Postal Code
SS0 0RY
Country
United Kingdom
Facility Name
Royal Hampshire County Hospital
City
Winchester
State/Province
England
ZIP/Postal Code
SO22 5DG
Country
United Kingdom
Facility Name
Western Infirmary
City
Glasgow
State/Province
Scotland
ZIP/Postal Code
G11 6NT
Country
United Kingdom
Facility Name
Beatson West of Scotland Cancer Centre
City
Glasgow
State/Province
Scotland
ZIP/Postal Code
G12 0YN
Country
United Kingdom
Facility Name
Hairmyres Hospital
City
Glasgow
State/Province
Scotland
ZIP/Postal Code
G12 0YN
Country
United Kingdom
Facility Name
Crosshouse Hospital
City
Kilmarnock
State/Province
Scotland
ZIP/Postal Code
KA2 OBE
Country
United Kingdom
Facility Name
Velindre Cancer Center at Velindre Hospital
City
Cardiff
State/Province
Wales
ZIP/Postal Code
CF14 2TL
Country
United Kingdom
Facility Name
Withybush General Hospital
City
Haverfordwest
State/Province
Wales
ZIP/Postal Code
SA61 2PZ
Country
United Kingdom
Facility Name
Royal Gwent Hospital
City
Newport Gwent
State/Province
Wales
ZIP/Postal Code
NP9 2UB
Country
United Kingdom
Facility Name
South West Wales Cancer Institute
City
Swansea
State/Province
Wales
ZIP/Postal Code
SA2 8QA
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs