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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00458796
• Other study ID #: CDR0000538879
• Secondary ID: NCRI-BISMARKISRC
• Status: Terminated
• Phase: N/A
• Start date: March 2006

Study information

• Verified date: May 2022
• Source: University of Leeds
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1500
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Hypercalcemia
• Hypercalcemia of Malignancy
• Metastatic Cancer
• Musculoskeletal Complications
• Neoplasms
• Pain

Intervention

Drug:
• zoledronic acid

Procedure:
• quality-of-life assessment

Locations

Country	Name	City	State
United Kingdom	Royal Bournemouth Hospital	Bournemouth	England
United Kingdom	Velindre Cancer Center at Velindre Hospital	Cardiff	Wales
United Kingdom	Derbyshire Royal Infirmary	Derby	England
United Kingdom	Doncaster Royal Infirmary	Doncaster	England
United Kingdom	University Hospital of North Durham	Durham	England
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow	Scotland
United Kingdom	Hairmyres Hospital	Glasgow	Scotland
United Kingdom	Western Infirmary	Glasgow	Scotland
United Kingdom	Diana Princess of Wales Hospital	Grimsby	England
United Kingdom	St. Luke's Cancer Centre at Royal Surrey County Hospital	Guildford	England
United Kingdom	Withybush General Hospital	Haverfordwest	Wales
United Kingdom	Huddersfield Royal Infirmary	Huddersfield, West Yorks	England
United Kingdom	Crosshouse Hospital	Kilmarnock	Scotland
United Kingdom	Royal Liverpool University Hospital	Liverpool	England
United Kingdom	Saint Bartholomew's Hospital	London	England
United Kingdom	Christie Hospital	Manchester	England
United Kingdom	Withington Hospital	Manchester	England
United Kingdom	Clatterbridge Centre for Oncology	Merseyside	England
United Kingdom	Royal Gwent Hospital	Newport Gwent	Wales
United Kingdom	George Eliot Hospital	Nuneaton	England
United Kingdom	Dorset Cancer Centre	Poole Dorset	England
United Kingdom	Scunthorpe General Hospital	Scunthorpe	England
United Kingdom	Cancer Research Centre at Weston Park Hospital	Sheffield	England
United Kingdom	Royal Shrewsbury Hospital	Shrewsbury	England
United Kingdom	Solihull Hospital	Solihull	England
United Kingdom	Southampton General Hospital	Southampton	England
United Kingdom	South West Wales Cancer Institute	Swansea	Wales
United Kingdom	South Warwickshire Hospital	Warwick, Warwickshire	England
United Kingdom	Southend University Hospital NHS Foundation Trust	Westcliff-On-Sea	England
United Kingdom	Royal Hampshire County Hospital	Winchester	England

Sponsors (2)

Lead Sponsor	Collaborator
University of Leeds	University of Sheffield

Country where clinical trial is conducted

United Kingdom, 

Outcome

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

External Links

•   Published trial results