Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Supportive care Completed 18 and over NCI SWOG-S0308 NCT00301886

Objectives

Primary

1. 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

1. Compare the change in patient-reported measures of pain and use of analgesics in patients treated with these drugs.
2. Compare the time to first clinically apparent SRE in patients treated with these drugs.
3. Compare the toxicity of these drugs.
4. Compare the changes in performance status and overall survival of patients treated with these drugs.

Entry Criteria

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

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

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

Expected Enrollment

A total of 488 patients will be accrued for this study.

Outcomes

Skeletal-related events (SRE)

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

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.

Trial Contact Information

Trial Lead Organizations

Southwest Oncology Group

Saul Rivkin, MD, Protocol chair		Ph: 206-386-2929 Email: saul.rivkin@swedish.org
Kathy Albain, MD, Protocol co-chair		Ph: 708-327-3304 Email: kalbain@lumc.edu
Dawn Hershman, MD, Protocol co-chair		Ph: 212-305-1945

Registry Information
Official Title		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
Trial Start Date		2006-05-16
Registered in ClinicalTrials.gov		NCT00301886
Date Submitted to PDQ		2006-01-05
Information Last Verified		2006-06-15