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 because the information has not been verified recently.
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
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 Recruiting
Bournemouth, England, United Kingdom, BH7 7DW
Contact: Tamas Hickish, MD    44-1202-704-789    tamas.hickish@rbch.nhs.uk   
Derbyshire Royal Infirmary Recruiting
Derby, England, United Kingdom, DE1 2QY
Contact: Pamela Woodings, MRCP, FRCR, MBCHB    44-1332-347-141 ext. 4575      
Doncaster Royal Infirmary Recruiting
Doncaster, England, United Kingdom, DN2 5LT
Contact: Doncaster Royal Infirmary    44-1302-366-666      
University Hospital of North Durham Recruiting
Durham, England, United Kingdom, DH1 5TW
Contact: Wendy Taylor, MD    44-19-333-2659      
Diana Princess of Wales Hospital Recruiting
Grimsby, England, United Kingdom, DN33 2BA
Contact: Sunil Upadhyay, MD    44-147-287-4111      
St. Luke's Cancer Centre at Royal Surrey County Hospital Recruiting
Guildford, England, United Kingdom, GU2 7XX
Contact: Stephen J. Houston, MD    44-1483-571-122 ext. 6744    stephen.houston@royalsurrey.nhs.uk   
Huddersfield Royal Infirmary Recruiting
Huddersfield, West Yorks, England, United Kingdom, HD3 3EA
Contact: Johnathan Joffe, MD    44-1484-342-150    jk.joffe@cht.nhs.uk   
Royal Liverpool University Hospital Recruiting
Liverpool, England, United Kingdom, L7 8XP
Contact: Susan M. O, MD    44-151-334-1155      
Saint Bartholomew's Hospital Recruiting
London, England, United Kingdom, EC1A 7BE
Contact: Christopher J. Gallagher, MD    44-20-7601-8521    chris.gallagher@bartsandthelondon.nhs.uk   
Christie Hospital Recruiting
Manchester, England, United Kingdom, M20 4BX
Contact: Andrew M. Wardley, MD    44-161-446-3746    andrew.wardley@christie-tr.nwest.nhs.uk   
Withington Hospital Recruiting
Manchester, England, United Kingdom, M20 8LR
Contact: Andrew M. Wardley, MD    44-161-611-3186      
Clatterbridge Centre for Oncology Recruiting
Merseyside, England, United Kingdom, CH63 4JY
Contact: Susan M. O, MD    44-151-334-1155    sue.oreilly@ccotrust.nhs.uk   
George Eliot Hospital Recruiting
Nuneaton, England, United Kingdom, CV10 7DJ
Contact: Lydia Fresco, MD    44-247-686-5512      
Dorset Cancer Centre Recruiting
Poole Dorset, England, United Kingdom, BH15 2JB
Contact: Susan Dean, MD    44-1202-442-491      
Scunthorpe General Hospital Recruiting
Scunthorpe, England, United Kingdom, DN15 7BH
Contact: Thiagarajan Sreenivasant    44-0172-428-2282 ext. 5144      
Cancer Research Centre at Weston Park Hospital Recruiting
Sheffield, England, United Kingdom, S1O 2SJ
Contact: Robert E. Coleman, MD, FRCP    44-114-226-5213    r.e.coleman@sheffield.ac.uk   
Royal Shrewsbury Hospital Recruiting
Shrewsbury, England, United Kingdom, SY3 8XQ
Contact: Rajiv K. Agrawal, MD    01743-261334    rajiv.agrawal@rsh.nhs.uk   
Solihull Hospital Recruiting
Solihull, England, United Kingdom, B91 2JL
Contact: Andrew Stockdale, MD    44-24-7696-7151      
Southampton General Hospital Recruiting
Southampton, England, United Kingdom, SO16 6YD
Contact: Peter Simmonds    44-23-8079-3627      
South Warwickshire Hospital Recruiting
Warwick, Warwickshire, England, United Kingdom, CV34 5BJ
Contact: David Jones, MD    44-24-7696-7151      
Southend University Hospital NHS Foundation Trust Recruiting
Westcliff-On-Sea, England, United Kingdom, SS0 0RY
Contact: Anne Robinson, MD    44-1702-221-226      
Royal Hampshire County Hospital Recruiting
Winchester, England, United Kingdom, SO22 5DG
Contact: Virginia Hall, MD    44-1962-863-535      
Beatson West of Scotland Cancer Centre Recruiting
Glasgow, Scotland, United Kingdom, G12 0YN
Contact: Jonathan Hicks, MD    44-169-836-6729    jonathan.hicks@northglasgow.scot.nhs.uk   
Hairmyres Hospital Recruiting
Glasgow, Scotland, United Kingdom, G12 0YN
Contact: Hosney M. A. Yosef, MD    44-141-301-7066      
Western Infirmary Recruiting
Glasgow, Scotland, United Kingdom, G11 6NT
Contact: Mohammed Rizwanullah, MD    44-0141-211-2860      
Crosshouse Hospital Recruiting
Kilmarnock, Scotland, United Kingdom, KA2 OBE
Contact: Diana Ritchie, MD    44-141-221-1724      
Velindre Cancer Center at Velindre Hospital Recruiting
Cardiff, Wales, United Kingdom, CF14 2TL
Contact: Peter J. Barrett Lee, MD    44-29-2031-6292      
Withybush General Hospital Recruiting
Haverfordwest, Wales, United Kingdom, SA61 2PZ
Contact: Gianfilippo Bertelli, MD, FRCPE    44-1437-764-545      
Royal Gwent Hospital Recruiting
Newport Gwent, Wales, United Kingdom, NP9 2UB
Contact: Christopher Gaffney, MD    44-163-323-4266      
South West Wales Cancer Institute Recruiting
Swansea, Wales, United Kingdom, SA2 8QA
Contact: Gianfilippo Bertelli, MD, FRCPE    44-179-228-5826    gianfilippo.bertelli@swansea-tr.wales.nhs.uk   
Sponsors and Collaborators
University of Leeds
Investigators
Study Chair: Robert E. Coleman, MD, FRCP Cancer Research Centre at Weston Park Hospital
  More Information

Additional Information:
No publications provided

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
Hypercalcemia
Neoplasm Metastasis
Neoplasms, Second Primary
Neoplasms by Site
Breast Diseases
Skin Diseases
Calcium Metabolism Disorders
Metabolic Diseases
Water-Electrolyte Imbalance
Neoplastic Processes
Pathologic Processes
Zoledronic acid
Diphosphonates
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 20, 2014