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

Condition(s) targeted: Breast Cancer; Hypercalcemia; Metastatic Cancer

Intervention: ibandronate sodium (Drug); zoledronic acid (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Wales Cancer Trials Unit

Official(s) and/or principal investigator(s):
Peter J. Barrett Lee, MD, Study Chair, Affiliation: Velindre NHS Trust

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.

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 [ZICE]

Study design: Treatment, Randomized, Open Label, Active Control

Primary outcome: Frequency and timing of skeletal-related events (SREs)

Secondary outcome:

Time to first SREs

Proportion of patients with SREs

Pain and analgesic score

Quality of life

Toxicity

Survival

Health resource usage and serum bone marker levels

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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)

Royal Glamorgan Hospital, Llantrisant CF72 8XR, United Kingdom; Recruiting
Contact Person, Phone: 44-144-344-3443

Alexandra Healthcare NHS, Redditch, Worcestershire, England B98 7UB, United Kingdom; Recruiting
Contact Person, Phone: 44-152-750-3030

Broomfield Hospital, Chelmsford, Essex, England CM1 7ET, United Kingdom; Recruiting
Contact Person, Phone: 44-12-4544-0761

Burnley General Hospital, Burnley, England BB10 2PQ, United Kingdom; Recruiting
Contact Person, Phone: 44-128-242-5071

Calderdale Royal Hospital, Halifax, England HX3 0PW, United Kingdom; Recruiting
Contact Person, Phone: 44-142-235-7171

Charing Cross Hospital, London, England W6 8RF, United Kingdom; Recruiting
Contact Person, Phone: 44-20-8846-1234

Clatterbridge Centre for Oncology, Wirral, England CH63 4JY, United Kingdom; Recruiting
Contact Person, Phone: 44-151-334-1155

Conquest Hospital, Saint Leonards-on-Sea, England TN37 7RD, United Kingdom; Recruiting
Contact Person, Phone: 44-14-2475-5255

Countess of Chester Hospital, Chester, England CH2 1UL, United Kingdom; Recruiting
Contact Person, Phone: 44-124-436-5000

Darent Valley Hospital, Dartford Kent, England DA2 8DA, United Kingdom; Recruiting
Contact Person, Phone: 44-132-242-8100

Derbyshire Royal Infirmary, Derby, England DE1 2QY, United Kingdom; Recruiting
Contact Person, Phone: 44-133-234-7141

Diana Princess of Wales Hospital, Grimsby, England DN33 2BA, United Kingdom; Recruiting
Contact Person, Phone: 44-147-287-4111

Dorset Cancer Centre, Poole Dorset, England BH15 2JB, United Kingdom; Recruiting
Contact Person, Phone: 44-120-266-5511

Dorset County Hospital, Dorchester, England DT1 2JY, United Kingdom; Recruiting
Contact Person, Phone: 44-130-525-1150

Essex County Hospital, Colchester, England C03 3NB, United Kingdom; Recruiting
Contact Person, Phone: 44-120-674-7474

George Eliot Hospital, Nuneaton, England CV10 7DJ, United Kingdom; Recruiting
Contact Person, Phone: 44-247-635-1351

Gloucestershire Oncology Centre at Cheltenham General Hospital, Cheltenham, England GL53 7AN, United Kingdom; Recruiting
Contact Person, Phone: 44-845-422-2222

Huddersfield Royal Infirmary, Huddersfield, West Yorks, England HD3 3EA, United Kingdom; Recruiting
Contact Person, Phone: 44-148-434-2000

Ipswich Hospital, Ipswich, England IP4 5PD, United Kingdom; Recruiting
Contact Person, Phone: 44-147-371-2233

Kent and Canterbury Hospital, Canterbury, England CT1 3NG, United Kingdom; Recruiting
Contact Person, Phone: 44-122-776-6877

King's Mills Hospital, Nottinghamshire, England NG17 4JL, United Kingdom; Recruiting
Contact Person, Phone: 44-162-362-2515

Macclesfield District General Hospital, Macclesfield, England SK10 3BL, United Kingdom; Recruiting
Contact Paerson, Phone: 44-162-542-1000

Maidstone Hospital, Maidstone, England ME16 9QQ, United Kingdom; Recruiting
Contact Person, Phone: 44-16-2272-9000

North Devon District Hospital, Barnstaple, England EX31 4JB, United Kingdom; Recruiting
Contact Person, Phone: 44-12-7132-2577

Nottingham City Hospital NHS Trust, Nottingham, England NG5 1PB, United Kingdom; Recruiting
Contact Person, Phone: 44-115-969-1169

Peterborough Hospitals Trust, Peterborough, England PE3 6DA, United Kingdom; Recruiting
Contact Person, Phone: 44-17-1187-4000

Portsmouth Oncology Centre at Saint Mary's Hospital, Portsmouth, England P03 6AD, United Kingdom; Recruiting
Contact Person, Phone: 44-23-9228-6000

Princess Royal Hospital at Hull and East Yorkshire NHS Trust, Hull, England HU8 9HE, United Kingdom; Recruiting
Contact Person, Phone: 44-148-270-1151

Queen Elizabeth Hospital, Gateshead, England NE9 7UD, United Kingdom; Recruiting
Contact Person, Phone: 44-191-482-0000

Queen Elizabeth The Queen Mother Hospital, Margate, England CT9 4AN, United Kingdom; Recruiting
Contact Person, Phone: 44-184-322-5544

Queen's Hospital, Burton-upon-Trent, England DE13 0RB, United Kingdom; Recruiting
Contact Person, Phone: 44-128-356-6333

Rosemere Cancer Centre at Royal Preston Hospital, Preston, England PR2 9HT, United Kingdom; Recruiting
Contact Person, Phone: 44-177-271-6565

Royal Albert Edward Infirmary, Wigan, England WN1 2NN, United Kingdom; Recruiting
Contact Person, Phone: 44-194-224-4000

Royal Bournemouth Hospital NHS Trust, Bournemouth, England BH7 7DW, United Kingdom; Recruiting
Contact Person, Phone: 44-120-230-3626

Royal Cornwall Hospital, Truro, Cornwall, England TR1 3LJ, United Kingdom; Recruiting
Contact Person, Phone: 44-187-225-0000

Royal Devon and Exeter Hospital, Exeter, England EX2 5DW, United Kingdom; Recruiting
Contact Person, Phone: 44-139-240-118

Royal Hampshire County Hospital, Winchester, England SO22 5DG, United Kingdom; Recruiting
Contact Person, Phone: 44-196-286-3535

Royal Liverpool University Hospital, Liverpool, England L7 8XP, United Kingdom; Recruiting
Contact Person, Phone: 44-151-334-1155

Royal Marsden - London, London, England SW3 6JJ, United Kingdom; Recruiting
Contact Person, Phone: 44-20-7352-8171

Royal Marsden - Surrey, Sutton, England SM2 5PT, United Kingdom; Recruiting
Contact Person, Phone: 44-20-8642-6011

Saint Bartholomew's Hospital, London, England EC1A 7BE, United Kingdom; Recruiting
Contact Person, Phone: 44-20-7377-7000

Scarborough General Hospital, Scarborough, England YO12 6QL, United Kingdom; Recruiting
Contact Person, Phone: 44-172-336-8111

Scunthorpe General Hospital, Scunthorpe, England ON15 7BH, United Kingdom; Recruiting
Contact Person, Phone: 44-172-428-2282

Solihull Hospital, Solihull, England B91 2JL, United Kingdom; Recruiting
Contact Person, Phone: 44-121-424-2000

South Tyneside District Hospital, Tyne & Wear, England NE34 0PL, United Kingdom; Recruiting
Contact Person, Phone: 44-844-811-3030

South Warwickshire Hospital, Warwick, Warwickshire, England CV34 5BW, United Kingdom; Recruiting
Contact Person, Phone: 44-192-649-5321

Southampton General Hospital, Southampton, England SO16 6YD, United Kingdom; Recruiting
Contact Person, Phone: 44-23-8077-7222

Southend University Hospital NHS Foundation Trust, Westcliff-On-Sea, England SS0 0RY, United Kingdom; Recruiting
Contact Person, Phone: 44-170-243-5555

St. George's Hospital, London, England SW17 0QT, United Kingdom; Recruiting
Contact Person, Phone: 44-20-8672-1255

St. Mary's Hospital, Newport, England PO30 5TG, United Kingdom; Recruiting
Contact Person, Phone: 44-198-352-4081

Torbay Hospital, Torquay Devon, England TQ2 7AA, United Kingdom; Recruiting
Contact Person, Phone: 44-180-361-4567

University Hospital of Hartlepool, Hartlepool, Cleveland, England TS24 9AH, United Kingdom; Recruiting
Contact Person, Phone: 44-142-926-6654

University Hospital of North Durham, Durham, England DH1 5TW, United Kingdom; Recruiting
Contact Person, Phone: 44-191-333-2333

University Hospital of North Tees, Stockton-On-Tees, England TS19 8PE, United Kingdom; Recruiting
Contact Person, Phone: 44-164-261-7617

Walsgrave Hospital, Coventry, England CV2 2DX, United Kingdom; Recruiting
Contact Person, Phone: 44-247-660-2020

Warrington Hospital NHS Trust, Warrington, England WA5 1QG, United Kingdom; Recruiting
Contact Person, Phone: 44-192-563-5911

Wexham Park Hospital, Slough, Berkshire, England SL2 4HL, United Kingdom; Recruiting
Contact Person, Phone: 44-175-363-3000

Whipps Cross Hospital, London, England E11 1NR, United Kingdom; Recruiting
Contact Person, Phone: 44-20-8539-5522

William Harvey Hospital, Ashford, England TN24 0LZ, United Kingdom; Recruiting
Contact Person, Phone: 44-123-363-3331

Worcester Royal Hospital, Worcester, England WR5 1AN, United Kingdom; Recruiting
Contact Person, Phone: 44-190-576-3333

Wycombe General Hospital, High Wycombe, England HP11 2TT, United Kingdom; Recruiting
Contact Person, Phone: 44-149-452-6161

Yeovil District Hospital, Yeovil - Somerset, England BA21 4AT, United Kingdom; Recruiting
Contact Person, Phone: 44-193-547-5122

Crosshouse Hospital, Kilmarnock, Scotland KA2 OBE, United Kingdom; Recruiting
Contact Person, Phone: 44-156-352-1133

Falkirk & District Royal Infirmary, Falkirk, Scotland FK1 5QE, United Kingdom; Recruiting
Contact Person, Phone: 44-132-462-4000

Hairmyres Hospital, East Kilbride, Scotland G75 8RG, United Kingdom; Recruiting
Contact Person, Phone: 44-135-558-5000

Western Infirmary, Glasgow, Scotland G11 6NT, United Kingdom; Recruiting
Contact Person, Phone: 44-141-211-2829

Wishaw General Hospital, Wishaw, Scotland ML2 0DP, United Kingdom; Recruiting
Contact Person, Phone: 44-169-836-1100

Bronglais District General Hospital, Aberystwyth, Wales SY23 1ER, United Kingdom; Recruiting
Contact Person, Phone: 44-19-7062-3131

Glan Clwyd Hospital, Rhyl, Denbighshire, Wales LL 18 5UJ, United Kingdom; Recruiting
Contact Person, Phone: 44-174-558-3910

Nevill Hall Hospital, Abergavenny, Wales NP7 7EG, United Kingdom; Recruiting
Contact Person, Phone: 44-187-373-2732

Prince Charles Hospital, Mid Glamorgan, Wales CF47 9DT, United Kingdom; Recruiting
Contact Person, Phone: 44-168-572-1721

Princess of Wales Hospital, Bridgend, Wales CF31 1JP, United Kingdom; Recruiting
Contact Person, Phone: 44-165-675-2752

Royal Gwent Hospital, Newport Gwent, Wales NP20 2UB, United Kingdom; Recruiting
Contact Person, Phone: 44-163-362-3623

South West Wales Cancer Institute, Swansea, Wales SA2 8QA, United Kingdom; Recruiting
Contact Person, Phone: 44-179-220-5666

Velindre Cancer Center at Velindre Hospital, Cardiff, Wales CF14 2TL, United Kingdom; Recruiting
Peter J. Barrett Lee, MD, Phone: 44-29-2031-6292

West Wales General Hospital, Carmarthen, Wales SA31 2AF, United Kingdom; Recruiting
Contact Person, Phone: 44-126-723-5151

Withybush General Hospital, Haverfordwest, Wales SA61 2PZ, United Kingdom; Recruiting
Contact Person, Phone: 44-143-774-4545

Wrexham Maelor Hospital, Wrexham, Wales LL13 7TD, United Kingdom; Recruiting
Contact Person, Phone: 44-197-829-1100

Ysbyty Gwynedd, Bangor, Wales LL57 2PW, United Kingdom; Recruiting
Contact Person, Phone: 44-124-838-4384

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: January 2006
Last updated: October 6, 2009