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

Sponsor

University of Leeds (Other)

Overall Status

Terminated

CT.gov ID

NCT00458796

Collaborator

University of Sheffield (Other)

1,500

Enrollment

Locations

Patients Per Site

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Hypercalcemia of Malignancy Metastatic Cancer Musculoskeletal Complications Pain	Drug: zoledronic acid Procedure: quality-of-life assessment	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

1500 participants

Allocation:

Randomized

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

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 Start Date :

Mar 1, 2006

Outcome Measures

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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

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