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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00326820
• Other study ID #: CDR0000478864
• Secondary ID: WCTU-ZICENCRI-ZI
• Status: Active, not recruiting
• Phase: Phase 3
• First received: May 16, 2006
• Last updated: March 12, 2013
• Start date: January 2006
• Est. completion date: October 2015

Study information

• Verified date: March 2013
• Source: Wales Cancer Trials Unit
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics CommitteeUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1404
• Est. completion date: October 2015
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Hypercalcemia
• Hypercalcemia of Malignancy
• Metastatic Cancer
• Neoplasm Metastasis
• Paraneoplastic Syndromes

Intervention

Drug:
• ibandronate sodium

• zoledronic acid

• Zolendronic Acid
Zoledronic acid 4 mg by intravenous infusion every 4 weeks.

Locations

Country	Name	City	State
United Kingdom	Nevill Hall Hospital	Abergavenny	Wales
United Kingdom	Bronglais District General Hospital	Aberystwyth	Wales
United Kingdom	William Harvey Hospital	Ashford	England
United Kingdom	Ysbyty Gwynedd	Bangor	Wales
United Kingdom	North Devon District Hospital	Barnstaple	England
United Kingdom	Royal Bournemouth Hospital	Bournemouth	England
United Kingdom	Princess of Wales Hospital	Bridgend	Wales
United Kingdom	Burnley General Hospital	Burnley	England
United Kingdom	Queen's Hospital	Burton-upon-Trent	England
United Kingdom	Kent and Canterbury Hospital	Canterbury	England
United Kingdom	Velindre Cancer Center at Velindre Hospital	Cardiff	Wales
United Kingdom	West Wales General Hospital	Carmarthen	Wales
United Kingdom	Broomfield Hospital	Chelmsford, Essex	England
United Kingdom	Gloucestershire Oncology Centre at Cheltenham General Hospital	Cheltenham	England
United Kingdom	Countess of Chester Hospital	Chester	England
United Kingdom	Essex County Hospital	Colchester	England
United Kingdom	Walsgrave Hospital	Coventry	England
United Kingdom	Darent Valley Hospital	Dartford Kent	England
United Kingdom	Derbyshire Royal Infirmary	Derby	England
United Kingdom	Dorset County Hospital	Dorchester	England
United Kingdom	University Hospital of North Durham	Durham	England
United Kingdom	Hairmyres Hospital	East Kilbride	Scotland
United Kingdom	Royal Devon and Exeter Hospital	Exeter	England
United Kingdom	Falkirk and District Royal Infirmary	Falkirk	Scotland
United Kingdom	Queen Elizabeth Hospital	Gateshead	England
United Kingdom	Western Infirmary	Glasgow	Scotland
United Kingdom	Diana Princess of Wales Hospital	Grimsby	England
United Kingdom	Calderdale Royal Hospital	Halifax	England
United Kingdom	University Hospital of Hartlepool	Hartlepool, Cleveland	England
United Kingdom	Withybush General Hospital	Haverfordwest	Wales
United Kingdom	Wycombe General Hospital	High Wycombe	England
United Kingdom	Huddersfield Royal Infirmary	Huddersfield, West Yorks	England
United Kingdom	Princess Royal Hospital at Hull and East Yorkshire NHS Trust	Hull	England
United Kingdom	Ipswich Hospital	Ipswich	England
United Kingdom	Crosshouse Hospital	Kilmarnock	Scotland
United Kingdom	Royal Liverpool University Hospital	Liverpool	England
United Kingdom	Royal Glamorgan Hospital	Llantrisant
United Kingdom	Charing Cross Hospital	London	England
United Kingdom	Royal Marsden - London	London	England
United Kingdom	Saint Bartholomew's Hospital	London	England
United Kingdom	St. George's Hospital	London	England
United Kingdom	Whipps Cross Hospital	London	England
United Kingdom	Macclesfield District General Hospital	Macclesfield	England
United Kingdom	Maidstone Hospital	Maidstone	England
United Kingdom	Queen Elizabeth The Queen Mother Hospital	Margate	England
United Kingdom	Prince Charles Hospital	Mid Glamorgan	Wales
United Kingdom	St. Mary's Hospital	Newport	England
United Kingdom	Royal Gwent Hospital	Newport Gwent	Wales
United Kingdom	Nottingham City Hospital	Nottingham	England
United Kingdom	King's Mills Hospital	Nottinghamshire	England
United Kingdom	George Eliot Hospital	Nuneaton	England
United Kingdom	Peterborough Hospitals Trust	Peterborough	England
United Kingdom	Dorset Cancer Centre	Poole Dorset	England
United Kingdom	Portsmouth Oncology Centre at Saint Mary's Hospital	Portsmouth	England
United Kingdom	Rosemere Cancer Centre at Royal Preston Hospital	Preston	England
United Kingdom	Alexandra Healthcare NHS	Redditch, Worcestershire	England
United Kingdom	Glan Clwyd Hospital	Rhyl, Denbighshire	Wales
United Kingdom	Conquest Hospital	Saint Leonards-on-Sea	England
United Kingdom	Scarborough General Hospital	Scarborough	England
United Kingdom	Scunthorpe General Hospital	Scunthorpe	England
United Kingdom	Wexham Park Hospital	Slough, Berkshire	England
United Kingdom	Solihull Hospital	Solihull	England
United Kingdom	Southampton General Hospital	Southampton	England
United Kingdom	University Hospital of North Tees	Stockton-On-Tees	England
United Kingdom	Royal Marsden - Surrey	Sutton	England
United Kingdom	South West Wales Cancer Institute	Swansea	Wales
United Kingdom	Torbay Hospital	Torquay Devon	England
United Kingdom	Royal Cornwall Hospital	Truro, Cornwall	England
United Kingdom	South Tyneside District Hospital	Tyne & Wear	England
United Kingdom	Warrington Hospital NHS Trust	Warrington	England
United Kingdom	South Warwickshire Hospital	Warwick, Warwickshire	England
United Kingdom	Southend University Hospital NHS Foundation Trust	Westcliff-On-Sea	England
United Kingdom	Royal Albert Edward Infirmary	Wigan	England
United Kingdom	Royal Hampshire County Hospital	Winchester	England
United Kingdom	Clatterbridge Centre for Oncology	Wirral	England
United Kingdom	Wishaw General Hospital	Wishaw	Scotland
United Kingdom	Worcester Royal Hospital	Worcester	England
United Kingdom	Wrexham Maelor Hospital	Wrexham	Wales
United Kingdom	Yeovil District Hospital	Yeovil - Somerset	England

Sponsors (2)

Lead Sponsor	Collaborator
Wales Cancer Trials Unit	Velindre NHS Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency and timing of skeletal-related events (SREs)		96 weeks	No
Secondary	Time to first SREs		96 Weeks	No
Secondary	Proportion of patients with SREs		96 Weeks	No
Secondary	Pain and analgesic score		96 weeks	No
Secondary	Quality of life		96 weeks	No
Secondary	Toxicity		96 weeks	Yes
Secondary	Survival		5 years	No
Secondary	Health resource usage and serum bone marker levels		96 weeks	No