Clinical trial NCT00458796: 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
Overall status: TERMINATED
Phase: NA
Conditions: 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
Lead sponsor: University of Leeds
Sponsor class: OTHER
Collaborators: name: University of Sheffield
First posted: 2007-04-11
Enrollment: 1500
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: SUPPORTIVE_CARE

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.

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

Primary outcomes:
measure: Fractures
measure: Radiotherapy to bone either for relief of pain or to treat or prevent pathological fractures or spinal cord compression
measure: Hypercalcemia of malignancy
measure: Orthopedic surgery to prevent or treat pathological fractures or spinal cord compression
measure: Spinal cord compression
Secondary outcomes:
measure: Quality of life as measured by QLQ-C30 and the QLQ-BR23 breast-specific module
measure: Clinical burden of skeletal complications
measure: Pain, performance status, and analgesic use
measure: Incidence of new bone metastases
measure: Overall survival
measure: Bisphosphonate use and expenditure on administration
measure: Health care utilization
measure: Clinical utility of the "point of care" test for N-telopeptides (NTx) excretion
Other outcomes:
Locations:
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
state: England
city: Derby
country: United Kingdom
facility: Derbyshire Royal Infirmary
state: England
city: Doncaster
country: United Kingdom
facility: Doncaster Royal Infirmary
state: England
city: Durham
country: United Kingdom
facility: University Hospital of North Durham
state: England
city: Grimsby
country: United Kingdom
facility: Diana Princess of Wales Hospital
state: England
city: Guildford
country: United Kingdom
facility: St. Luke's Cancer Centre at Royal Surrey County Hospital
state: England
city: Huddersfield, West Yorks
country: United Kingdom
facility: Huddersfield Royal Infirmary
state: England
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
state: England
city: London
country: United Kingdom
facility: Saint Bartholomew's Hospital
state: England
city: Manchester
country: United Kingdom
facility: Christie Hospital
state: England
city: Manchester
country: United Kingdom
facility: Withington Hospital
state: England
city: Merseyside
country: United Kingdom
facility: Clatterbridge Centre for Oncology
state: England
city: Nuneaton
country: United Kingdom
facility: George Eliot Hospital
state: England
city: Poole Dorset
country: United Kingdom
facility: Dorset Cancer Centre
state: England
city: Scunthorpe
country: United Kingdom
facility: Scunthorpe General Hospital
state: England
city: Sheffield
country: United Kingdom
facility: Cancer Research Centre at Weston Park Hospital
state: England
city: Shrewsbury
country: United Kingdom
facility: Royal Shrewsbury Hospital
state: England
city: Solihull
country: United Kingdom
facility: Solihull Hospital
state: England
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: England
city: Warwick, Warwickshire
country: United Kingdom
facility: South Warwickshire Hospital
state: England
city: Westcliff-On-Sea
country: United Kingdom
facility: Southend University Hospital NHS Foundation Trust
state: England
city: Winchester
country: United Kingdom
facility: Royal Hampshire County Hospital
state: England
city: Glasgow
country: United Kingdom
facility: Western Infirmary
state: Scotland
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
state: Scotland
city: Glasgow
country: United Kingdom
facility: Hairmyres Hospital
state: Scotland
city: Kilmarnock
country: United Kingdom
facility: Crosshouse Hospital
state: Scotland
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Center at Velindre Hospital
state: Wales
city: Haverfordwest
country: United Kingdom
facility: Withybush General Hospital
state: Wales
city: Newport Gwent
country: United Kingdom
facility: Royal Gwent Hospital
state: Wales
city: Swansea
country: United Kingdom
facility: South West Wales Cancer Institute
state: Wales
Study officials:
affiliation: Cancer Research Centre at Weston Park Hospital
name: Robert E. Coleman, MD, FRCP
role: STUDY_CHAIR
References: