S0308 Zoledronate or Ibandronate in Preventing Bone Problems in Women With Stage IV Breast Cancer That Has Spread to the Bone

Study Overview
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Brief Summary
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RATIONALE: Zoledronate and ibandronate may prevent or help relieve bone pain and other symptoms caused by bone metastases. It is not yet known whether zoledronate is more effective than ibandronate in preventing bone problems caused by bone metastases due to breast cancer. PURPOSE: This randomized phase III trial is studying zoledronate to see how well it works compared to ibandronate in preventing bone problems in women with stage IV breast cancer that has spread to the bone.

Detailed Description
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OBJECTIVES: Primary Compare the efficacy of zoledronate vs ibandronate, in terms of preventing the occurrence of skeletal-related events (SRE) (e.g., fracture, spinal cord compression, radiotherapy or surgery for bone symptoms or events, or hypercalcemia ≥ grade 3), in women with stage IV breast cancer and bone metastases. Secondary Compare the change in patient-reported measures of pain and use of analgesics in patients treated with these drugs. Compare the time to first clinically apparent SRE in patients treated with these drugs. Compare the toxicity of these drugs. Compare the changes in performance status and overall survival of patients treated with these drugs. OUTLINE: This is a multicenter, randomized study. Patients are stratified according to hormone receptor status (estrogen receptor [ER] and progesterone receptor [PR] negative vs ER and/or PR positive) and current evidence of fracture (vertebral or nonvertebral) or spinal compression (yes vs no). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral ibandronate once daily on days 1-28. Arm II: Patients receive zoledronate IV over 15 minutes on day 1. In both arms, treatment repeats every 28 days for up to 18 courses in the absence of unacceptable toxicity. Quality of life and pain are assessed at baseline, every 3 courses during study treatment, and at the end of study treatment. After completion of study treatment, patients are followed periodically for up to 3 years. PROJECTED ACCRUAL: A total of 488 patients will be accrued for this study.

Official Title
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A Phase III Randomized, Multicenter Non-Inferiority Trial Evaluating the Efficacy of Oral Ibandronate Versus Intravenous Zoledronate in the Reduction of Skeletal-Related Events in Patients With Metastatic Breast Cancer

Conditions
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Breast Cancer, Hypercalcemia of Malignancy, Metastatic Cancer, Pain

Intervention / Treatment
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* Drug: ibandronate
* Drug: zoledronate
* Procedure: quality-of-life assessment


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed stage IV breast cancer at primary diagnosis or at recurrence Any T, any N, M1 At least 1 dominant osteolytic or osteoblastic or mixed metastatic lesion outside any prior radiation field Lesion measures ≥ 1.0 cm by x-ray, CT scan, and/or MRI Controlled asymptomatic brain metastases allowed Controlled bone pain, defined as a physician/health care provider rating of ≤ grade 2 pain-SELECT (Bone) on the NCI CTC for Adverse Events Version 3.0 rating scale, required Current evidence of vertebral or nonvertebral fractures or spinal compression due to cancer, as determined by the treating physician, allowed No Paget's disease of the bone Estrogen receptor (ER) or progesterone receptor (PR) status known PATIENT CHARACTERISTICS: Female patient Menopausal status not specified Zubrod performance status 0-2 Creatinine normal Creatinine clearance ≥ 60 mL/min Serum calcium < 12 mg/dL Not pregnant or nursing Fertile patients must use effective contraception Must be able to receive IV medication and oral medication (i.e., must have physical integrity of the upper gastrointestinal tract) No malabsorption syndrome No primary hyperparathyroidism No known history of aspirin-sensitive asthma No other prior malignancy except for the following: Adequately treated basal cell or squamous cell skin cancer In situ cervical cancer Adequately treated stage I or II cancer currently in complete remission Any other cancer for which the patient has been disease-free for at least 5 years No uncontrolled medical illness or infection, including, but not limited to, the following: Unstable angina Recent myocardial infarction Life-threatening cardiac arrhythmia PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior bisphosphonates for metastatic bone disease More than 28 days since prior aminoglycoside antibiotics At least 28 days since prior oral bisphosphonates for osteoporosis More than 6 months since prior bisphosphonates used for adjuvant therapy Concurrent treatment, including chemotherapy, hormonal therapy, and/or biologic therapy for metastatic breast cancer allowed No concurrent participation in another clinical treatment trial for this cancer unless the patient is no longer receiving the intervention and is in the follow-up phase of the other clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: zoledronate<br>zoledronate | Drug: zoledronate<br> <br> * Other names: zoledronic acid;Procedure: quality-of-life assessment<br> <br> |
| Experimental: ibandronate<br>ibandronate | Drug: ibandronate<br> <br> * Other names: ibandronate sodium;Procedure: quality-of-life assessment<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Skeletal-related events (SRE) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in patient's rating of worst pain as measured by the Brief Pain Inventory |  |  | 
| Survival and time to first clinically apparent SRE |  |  | 
| Tolerability and toxicity as measured by NCI CTCAE v3.0 |  |  | 
| Changes in performance status |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pain, hypercalcemia of malignancy, stage IV breast cancer, bone metastases, recurrent breast cancer