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

March 12, 2013 updated by: Wales Cancer Trials Unit

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

1404

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • Zoledronate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Frequency and timing of skeletal-related events (SREs)
Time Frame: 96 weeks
96 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Survival
Time Frame: 5 years
5 years
Time to first SREs
Time Frame: 96 Weeks
96 Weeks
Proportion of patients with SREs
Time Frame: 96 Weeks
96 Weeks
Pain and analgesic score
Time Frame: 96 weeks
96 weeks
Quality of life
Time Frame: 96 weeks
96 weeks
Toxicity
Time Frame: 96 weeks
96 weeks
Health resource usage and serum bone marker levels
Time Frame: 96 weeks
96 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Wales Cancer Trials Unit

Collaborators

Velindre NHS Trust

Investigators

  • Study Chair: Peter J. Barrett Lee, MD, Velindre NHS Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2006

Primary Completion (Actual)

December 1, 2012

Study Completion (Anticipated)

October 1, 2015

Study Registration Dates

First Submitted

May 16, 2006

First Submitted That Met QC Criteria

May 16, 2006

First Posted (Estimate)

May 17, 2006

Study Record Updates

Last Update Posted (Estimate)

March 13, 2013

Last Update Submitted That Met QC Criteria

March 12, 2013

Last Verified

March 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000478864
  • WCTU-ZICE
  • NCRI-ZICE
  • ROCHE-ZICE
  • ISRCTN13914201
  • EU-20613
  • EUDRACT-2005-001710-40

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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