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

NCT ID: NCT00301886

Last Updated: 2013-11-13

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-05-31
• Study Completion Date: 2006-05-31

Brief Summary

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

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.

Conditions

Breast Cancer; Hypercalcemia of Malignancy; Metastatic Cancer; Pain

Keywords

pain; hypercalcemia of malignancy; stage IV breast cancer; bone metastases; recurrent breast cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

zoledronate

zoledronate

Group Type: EXPERIMENTAL

zoledronate

Intervention Type: DRUG

quality-of-life assessment

Intervention Type: PROCEDURE

ibandronate

ibandronate

Group Type: EXPERIMENTAL

ibandronate

Intervention Type: DRUG

quality-of-life assessment

Intervention Type: PROCEDURE

Interventions

ibandronate

Intervention Type: DRUG

zoledronate

Intervention Type: DRUG

quality-of-life assessment

Intervention Type: PROCEDURE

Other Intervention Names

ibandronate sodium; zoledronic acid

Eligibility Criteria

Inclusion 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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

SWOG Cancer Research Network

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Saul E. Rivkin, MD

Role: STUDY_CHAIR

Swedish Cancer Institute at Swedish Medical Center - First Hill Campus

Kathy S. Albain, MD

Role: STUDY_CHAIR

Loyola University

Dawn Hershman, MD

Role: STUDY_CHAIR

Herbert Irving Comprehensive Cancer Center

Other Identifiers

S0308

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA037429

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000463758

Identifier Type: -

Identifier Source: org_study_id