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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00326820

  Show 79 Study Locations
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
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 April 15, 2014