Ibandronate or Zoledronate in Treating Patients With Newly Diagnosed Bone Metastases From Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Velindre NHS Trust
Information provided by (Responsible Party):
Wales Cancer Trials Unit
ClinicalTrials.gov Identifier:
NCT00326820
First received: May 16, 2006
Last updated: March 12, 2013
Last verified: March 2013
  Purpose

RATIONALE: Ibandronate and zoledronate may help relieve some of the symptoms caused by bone metastases. It is not yet know whether ibandronate is more effective than zoledronate in treating bone metastases from breast cancer.

PURPOSE: This randomized phase III trial is studying ibandronate to see how well it works compared with zoledronate in treating patients with newly diagnosed bone metastases from breast cancer.


Condition Intervention Phase
Breast Cancer
Hypercalcemia of Malignancy
Metastatic Cancer
Drug: ibandronate sodium
Drug: zoledronic acid
Drug: Zolendronic Acid
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Zoledronate Versus Ibandronate Comparative Evaluation: A Randomized Phase III, Open-Label, Multicenter, Parallel Group Clinical Trial to Evaluate and Compare the Efficacy, Safety Profile and Tolerability of Oral Ibandronate Versus Intravenous Zoledronate in the Treatment of Breast Cancer Patients With Bone Metastases

Resource links provided by NLM:


Further study details as provided by Wales Cancer Trials Unit:

Primary Outcome Measures:
  • Frequency and timing of skeletal-related events (SREs) [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to first SREs [ Time Frame: 96 Weeks ] [ Designated as safety issue: No ]
  • Proportion of patients with SREs [ Time Frame: 96 Weeks ] [ Designated as safety issue: No ]
  • Pain and analgesic score [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
  • Quality of life [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
  • Survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Health resource usage and serum bone marker levels [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]

Enrollment: 1404
Study Start Date: January 2006
Estimated Study Completion Date: October 2015
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ibandronic Acid
50mg tablet once daily over 96 weeks
Drug: ibandronate sodium
Active Comparator: Zoledronic Acid
4 mg via intravenous infusion (iv) over a minimum of 15 minutes in at least 100mls of saline every 4 weeks over 96 weeks
Drug: zoledronic acid Drug: Zolendronic Acid
Zoledronic acid 4 mg by intravenous infusion every 4 weeks.
Other Name: Zoledronate

Detailed Description:

OBJECTIVES:

Primary

  • Compare the efficacy, in terms of reducing frequency and timing of skeletal-related events (SREs), of ibandronate vs zoledronate in patients with newly diagnosed bone metastases secondary to breast cancer.

Secondary

  • Compare the median time to first SRE in patients treated with these regimens.
  • Compare the percentage of patients experiencing a SRE after treatment with these regimens.
  • Compare the number of occult vertebral fractures present in patients at the end of treatment with these regimens.
  • Compare the pain and analgesic scores and quality of life of patients treated with these regimens.
  • Compare the number of patients developing renal dysfunction or hypocalcemia during the study period.
  • Compare the number of patients developing osteonecrosis of the jaw during study treatment and follow-up.
  • Compare the overall survival of these patients at 96 weeks and at 5 years.
  • Compare the health-resource usage of patients treated with these regimens.

OUTLINE: This is a randomized, open-label, parallel-group, controlled, multicenter study. Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive zoledronate IV over 15 minutes on day 1. Treatment repeats every 21* or 28 days for at least 96 weeks (24 or 32 courses) in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients who receive concurrent chemotherapy every 3 weeks receive study treatment every 21 days

  • Arm II: Patients receive oral ibandronate once daily on days 1-28. Treatment repeats every 28 days for at least 96 weeks (24 courses) in the absence of disease progression or unacceptable toxicity. Patients with bone pain or hypercalcemia at study entry or those who require IV therapy due to hypercalcemia while on study may receive 1 treatment with ibandronate IV at the discretion of the supervising clinician.

Quality of life and pain are assessed at baseline, after every 3 courses, and at completion of study treatment.

After completion of study treatment, patients are followed annually for up to 3 years.

PROJECTED ACCRUAL: A total of 1,400 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 proven breast cancer

    • Metastatic disease
    • Previous relapsed disease in sites other than bone allowed
  • Newly diagnosed multiple bone metastases within the past 3 months, meeting all of the following criteria:

    • Painful or asymptomatic
    • Lytic, mixed, or purely sclerotic type
    • Radiological diagnosis
    • IV bisphosphonate therapy indicated
  • No CNS metastases
  • Hormone receptor status not specified

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Male or female
  • Menopausal status not specified
  • No known active peptic ulcer
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No active dental problems, including infection of the teeth or jawbone (maxilla or mandible) or dental or fixture trauma
  • No prior or current diagnosis of osteonecrosis of the jaw, exposed bone in the mouth, or slow healing after dental procedures
  • Creatinine clearance ≥ 30 mL/min
  • Bilirubin ≤ 1.5 x upper limit of normal (ULN)
  • AST and ALT ≤ 1.5 times ULN
  • No history of bisphosphonate hypersensitivity
  • Able to comply with instructions relating to oral study medications
  • Able to take oral study medications
  • No psychiatric illness or other condition that would preclude giving informed consent

PRIOR CONCURRENT THERAPY:

  • At least 6 months since prior bisphosphonate therapy
  • At least 6 weeks since prior and no concurrent dental or jaw surgery (e.g., extractions or implants)

    • Concurrent unplanned dental extractions allowed provided study medication is discontinued for 8 weeks before and after the surgery
  • Concurrent chemotherapy and/or hormone therapy for metastatic disease allowed
  • No concurrent medications that affect bone metabolism (e.g., calcitonin or other nontrial bisphosphonates)
  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: NCT00326820

  Hide Study Locations
Locations
United Kingdom
William Harvey Hospital
Ashford, England, United Kingdom, TN24 0LZ
North Devon District Hospital
Barnstaple, England, United Kingdom, EX31 4JB
Royal Bournemouth Hospital
Bournemouth, England, United Kingdom, BH7 7DW
Burnley General Hospital
Burnley, England, United Kingdom, BB10 2PQ
Queen's Hospital
Burton-upon-Trent, England, United Kingdom, DE13 0RB
Kent and Canterbury Hospital
Canterbury, England, United Kingdom, CT1 3NG
Broomfield Hospital
Chelmsford, Essex, England, United Kingdom, CM1 7ET
Gloucestershire Oncology Centre at Cheltenham General Hospital
Cheltenham, England, United Kingdom, GL53 7AN
Countess of Chester Hospital
Chester, England, United Kingdom, CH2 1UL
Essex County Hospital
Colchester, England, United Kingdom, C03 3NB
Walsgrave Hospital
Coventry, England, United Kingdom, CV2 2DX
Darent Valley Hospital
Dartford Kent, England, United Kingdom, DA2 8DA
Derbyshire Royal Infirmary
Derby, England, United Kingdom, DE1 2QY
Dorset County Hospital
Dorchester, England, United Kingdom, DT1 2JY
University Hospital of North Durham
Durham, England, United Kingdom, DH1 5TW
Royal Devon and Exeter Hospital
Exeter, England, United Kingdom, EX2 5DW
Queen Elizabeth Hospital
Gateshead, England, United Kingdom, NE9 7UD
Diana Princess of Wales Hospital
Grimsby, England, United Kingdom, DN33 2BA
Calderdale Royal Hospital
Halifax, England, United Kingdom, HX3 0PW
University Hospital of Hartlepool
Hartlepool, Cleveland, England, United Kingdom, TS24 9AH
Wycombe General Hospital
High Wycombe, England, United Kingdom, HP11 2TT
Huddersfield Royal Infirmary
Huddersfield, West Yorks, England, United Kingdom, HD3 3EA
Princess Royal Hospital at Hull and East Yorkshire NHS Trust
Hull, England, United Kingdom, HU8 9HE
Ipswich Hospital
Ipswich, England, United Kingdom, IP4 5PD
Royal Liverpool University Hospital
Liverpool, England, United Kingdom, L7 8XP
Royal Marsden - London
London, England, United Kingdom, SW3 6JJ
St. George's Hospital
London, England, United Kingdom, SW17 0QT
Saint Bartholomew's Hospital
London, England, United Kingdom, EC1A 7BE
Charing Cross Hospital
London, England, United Kingdom, W6 8RF
Whipps Cross Hospital
London, England, United Kingdom, E11 1NR
Macclesfield District General Hospital
Macclesfield, England, United Kingdom, SK10 3BL
Maidstone Hospital
Maidstone, England, United Kingdom, ME16 9QQ
Queen Elizabeth The Queen Mother Hospital
Margate, England, United Kingdom, CT9 4AN
St. Mary's Hospital
Newport, England, United Kingdom, PO30 5TG
Nottingham City Hospital
Nottingham, England, United Kingdom, NG5 1PB
King's Mills Hospital
Nottinghamshire, England, United Kingdom, NG17 4JL
George Eliot Hospital
Nuneaton, England, United Kingdom, CV10 7DJ
Peterborough Hospitals Trust
Peterborough, England, United Kingdom, PE3 6DA
Dorset Cancer Centre
Poole Dorset, England, United Kingdom, BH15 2JB
Portsmouth Oncology Centre at Saint Mary's Hospital
Portsmouth, England, United Kingdom, P03 6AD
Rosemere Cancer Centre at Royal Preston Hospital
Preston, England, United Kingdom, PR2 9HT
Alexandra Healthcare NHS
Redditch, Worcestershire, England, United Kingdom, B98 7UB
Conquest Hospital
Saint Leonards-on-Sea, England, United Kingdom, TN37 7RD
Scarborough General Hospital
Scarborough, England, United Kingdom, YO12 6QL
Scunthorpe General Hospital
Scunthorpe, England, United Kingdom, ON15 7BH
Wexham Park Hospital
Slough, Berkshire, England, United Kingdom, SL2 4HL
Solihull Hospital
Solihull, England, United Kingdom, B91 2JL
Southampton General Hospital
Southampton, England, United Kingdom, SO16 6YD
University Hospital of North Tees
Stockton-On-Tees, England, United Kingdom, TS19 8PE
Royal Marsden - Surrey
Sutton, England, United Kingdom, SM2 5PT
Torbay Hospital
Torquay Devon, England, United Kingdom, TQ2 7AA
Royal Cornwall Hospital
Truro, Cornwall, England, United Kingdom, TR1 3LJ
South Tyneside District Hospital
Tyne & Wear, England, United Kingdom, NE34 0PL
Warrington Hospital NHS Trust
Warrington, England, United Kingdom, WA5 1QG
South Warwickshire Hospital
Warwick, Warwickshire, England, United Kingdom, CV34 5BW
Southend University Hospital NHS Foundation Trust
Westcliff-On-Sea, England, United Kingdom, SS0 0RY
Royal Albert Edward Infirmary
Wigan, England, United Kingdom, WN1 2NN
Royal Hampshire County Hospital
Winchester, England, United Kingdom, SO22 5DG
Clatterbridge Centre for Oncology
Wirral, England, United Kingdom, CH63 4JY
Worcester Royal Hospital
Worcester, England, United Kingdom, WR5 1AN
Yeovil District Hospital
Yeovil - Somerset, England, United Kingdom, BA21 4AT
Hairmyres Hospital
East Kilbride, Scotland, United Kingdom, G75 8RG
Falkirk and District Royal Infirmary
Falkirk, Scotland, United Kingdom, FK1 5QE
Western Infirmary
Glasgow, Scotland, United Kingdom, G11 6NT
Crosshouse Hospital
Kilmarnock, Scotland, United Kingdom, KA2 OBE
Wishaw General Hospital
Wishaw, Scotland, United Kingdom, ML2 0DP
Nevill Hall Hospital
Abergavenny, Wales, United Kingdom, NP7 7EG
Bronglais District General Hospital
Aberystwyth, Wales, United Kingdom, SY23 1ER
Ysbyty Gwynedd
Bangor, Wales, United Kingdom, LL57 2PW
Princess of Wales Hospital
Bridgend, Wales, United Kingdom, CF31 1JP
Velindre Cancer Center at Velindre Hospital
Cardiff, Wales, United Kingdom, CF14 2TL
West Wales General Hospital
Carmarthen, Wales, United Kingdom, SA31 2AF
Withybush General Hospital
Haverfordwest, Wales, United Kingdom, SA61 2PZ
Prince Charles Hospital
Mid Glamorgan, Wales, United Kingdom, CF47 9DT
Royal Gwent Hospital
Newport Gwent, Wales, United Kingdom, NP20 2UB
Glan Clwyd Hospital
Rhyl, Denbighshire, Wales, United Kingdom, LL 18 5UJ
South West Wales Cancer Institute
Swansea, Wales, United Kingdom, SA2 8QA
Wrexham Maelor Hospital
Wrexham, Wales, United Kingdom, LL13 7TD
Royal Glamorgan Hospital
Llantrisant, United Kingdom, CF72 8XR
Sponsors and Collaborators
Wales Cancer Trials Unit
Velindre NHS Trust
Investigators
Study Chair: Peter J. Barrett Lee, MD Velindre NHS Trust
  More Information

Additional Information:
No publications provided by Wales Cancer Trials Unit

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Wales Cancer Trials Unit
ClinicalTrials.gov Identifier: NCT00326820     History of Changes
Other Study ID Numbers: CDR0000478864, WCTU-ZICE, NCRI-ZICE, ROCHE-ZICE, ISRCTN13914201, EU-20613, EUDRACT-2005-001710-40
Study First Received: May 16, 2006
Last Updated: March 12, 2013
Health Authority: United Kingdom: Research Ethics Committee
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Wales Cancer Trials Unit:
hypercalcemia of malignancy
stage IV breast cancer
bone metastases
recurrent breast cancer
male breast cancer

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

ClinicalTrials.gov processed this record on August 28, 2014