S0307 Phase III Trial of Bisphosphonates as Adjuvant Therapy for Primary Breast Cancer.
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: clodronate disodium; ibandronate sodium; zoledronic acid
Intervention description: Given orally; Given orally; Given IV
Intervention MeSH terms: Zoledronic Acid; Ibandronic Acid; Clodronic Acid
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 6097.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage I breast cancer; stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer

Summary:

      RATIONALE: Zoledronate, clodronate, or ibandronate may delay or prevent bone metastases in
      patients with nonmetastatic breast cancer. It is not yet known whether zoledronate is more
      effective than clodronate or ibandronate in treating breast cancer.

      PURPOSE: This randomized phase III trial is studying zoledronate to see how well it works
      compared to clodronate or ibandronate in treating women who have undergone surgery for stage
      I, stage II, or stage III breast cancer.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically confirmed primary adenocarcinoma of the breast

               -  Stage I-III disease

               -  No evidence of metastatic disease

          -  Must have undergone lumpectomy or total mastectomy for primary disease within the past
             12 weeks, or have completed chemotherapy within the past 8 weeks

               -  Axillary evaluation per institutional standards

          -  Currently receiving or planning to receive standard adjuvant systemic therapy
             comprising chemotherapy, hormonal therapy, or combined chemotherapy/hormonal therapy
             for breast cancer

               -  Patients who are at low risk for disease recurrence and for whom adjuvant
                  systemic therapy will not be prescribed are not eligible

               -  Patients who receive biologic agents only or local radiotherapy only (without
                  chemotherapy and/or hormone therapy) are not eligible

               -  Additional therapies are allowed including radiotherapy and biologic agents
                  (e.g., trastuzumab [Herceptin^®], bevacizumab, or hematopoietic growth factors)

               -  Neoadjuvant therapy or hormonal therapy alone is allowed provided study entry
                  occurs ≥ 12 weeks after completion of surgery

          -  Patients with skeletal pain are eligible provided bone scan and/or roentgenological
             exam are negative for metastatic disease

               -  Suspicious findings must be confirmed as benign by x-ray, MRI, or biopsy

          -  Hormone receptor status:

               -  Not specified

        PATIENT CHARACTERISTICS:

        Age

          -  18 and over

        Sex

          -  Female

        Menopausal status

          -  Not specified

        Performance status

          -  Zubrod 0-2

        Life expectancy

          -  Not specified

        Hematopoietic

          -  Not specified

        Hepatic

          -  Not specified

        Renal

          -  Creatinine ≤ 2 times upper limit of normal

          -  Creatinine clearance ≥ 30 mL/min

          -  No renal failure

        Other

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  No history of esophageal stricture or motility disorders

               -  Gastroesophageal reflux disorder allowed

          -  No other malignancy within the past 5 years except adequately treated basal cell or
             squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated
             stage I or II cancer in complete remission

        PRIOR CONCURRENT THERAPY:

        Biologic therapy

          -  Prior or concurrent hematopoietic growth factors allowed

          -  HER-2-targeted therapies allowed

          -  Antiangiogenics allowed

        Chemotherapy

          -  See Disease Characteristics

        Endocrine therapy

          -  See Disease Characteristics

        Radiotherapy

          -  Concurrent radiotherapy to the breast, chest wall, or lymph node group allowed at the
             discretion of the treating physician

        Surgery

          -  See Disease Characteristics

        Other

          -  Prior neoadjuvant therapy allowed

          -  Prior bisphosphonates for bone density allowed

          -  No other concurrent bisphosphonates as adjuvant therapy or for treatment of
             osteoporosis

          -  No concurrent enrollment in clinical trials with bone density as an endpoint

               -  Concurrent enrollment on any other locoregional or systemic therapy breast cancer
                  study (including cooperative group studies) allowed