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

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified November 2007 by National Cancer Institute (NCI).
Recruitment status was:  Recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00458796
First received: April 9, 2007
Last updated: August 23, 2013
Last verified: November 2007
  Purpose

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 Intervention
Breast Cancer
Hypercalcemia of Malignancy
Metastatic Cancer
Musculoskeletal Complications
Pain
Drug: zoledronic acid
Procedure: quality-of-life assessment

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

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

Estimated Enrollment: 1500
Study Start Date: March 2006
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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00458796

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

ClinicalTrials.gov Identifier: NCT00458796     History of Changes
Other Study ID Numbers: CDR0000538879  NCRI-BISMARK  ISRCTN83586728  EU-20716  EUDRACT-2005-001376-12 
Study First Received: April 9, 2007
Last Updated: August 23, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
hypercalcemia of malignancy
musculoskeletal complications
pain
stage IV breast cancer
male breast cancer
recurrent breast cancer
bone metastases

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Neoplasm Metastasis
Hypercalcemia
Paraneoplastic Syndromes
Neoplasms by Site
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Calcium Metabolism Disorders
Metabolic Diseases
Water-Electrolyte Imbalance
Zoledronic acid
Diphosphonates
Bone Density Conservation Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on December 09, 2016