Zoledronic Acid in Treating Patients With Metastatic Breast Cancer, Metastatic Prostate Cancer, or Multiple Myeloma With Bone Involvement
Zoledronic Acid in Treating Patients With Metastatic Breast Cancer, Metastatic Prostate Cancer, or Multiple Myeloma With Bone Involvement
This randomized phase III trial studies two different schedules of zoledronic acid to compare
 how well they work in reducing bone-related complications in patients with breast cancer,
 prostate cancer, or multiple myeloma that has spread to other places in the body and have
 bone involvement. Bone-related complications are a major cause of morbidity in patients with
 metastatic prostate cancer, breast cancer, and multiple myeloma. Zoledronic acid may stop the
 growth of cancer cells in the bone and may help relieve some of the symptoms caused by bone
 metastases. It is not yet known whether giving zoledronic acid more or less frequently is
 more effective in treating patients with metastatic cancer that has spread to the bone.
PRIMARY OBJECTIVES:

 I. To determine whether every-12-week therapy with zoledronic acid is not inferior to
 every-4-week therapy for patients with metastatic breast cancer, metastatic prostate cancer,
 or multiple myeloma involving bone, as measured by the proportion who experience at least one
 skeletal related event within 24 months after randomization.

 SECONDARY OBJECTIVES:

 I. To compare pain scores (Brief Pain Inventory) of patients with metastatic breast cancer,
 metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of
 zoledronic acid to those receiving every 4 week dosing.

 II. To compare the functional status (Eastern Cooperative Oncology Group [ECOG] performance
 status) of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma
 involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4
 week dosing.

 III. To compare the incidence of osteonecrosis of the jaw in patients with metastatic breast
 cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing
 of zoledronic acid to those receiving every 4 week dosing.

 IV. To compare the incidence of renal dysfunction in patients with metastatic breast cancer,
 metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of
 zoledronic acid to those receiving every 4 week dosing.

 V. To compare the skeletal morbidity rate of these patients, defined as the number of
 skeletal-related events per year, of patients receiving every 12 week dosing to those
 receiving every 4 week dosing.

 VI. To compare the suppression of serum markers of bone resorption of patients with
 metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving
 every 12 week dosing of zoledronic acid to those receiving every 4 week dosing.

 VII. To determine whether every 12 week therapy with zoledronic acid is not inferior to
 every-4-week therapy for each subgroup of patients with either breast cancer, prostate
 cancer, or multiple myeloma, as measured by the proportion who experience at least one
 skeletal related event within 24 months after randomization.

 OUTLINE: Patients are randomized to 1 of 2 treatment arms.

 ARM I: Patients receive zoledronic acid intravenously (IV) over at least 15 minutes every 4
 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.

 ARM II: Patients receive zoledronic acid IV over at least 15 minutes every 12 weeks for up to
 2 years in the absence of disease progression or unacceptable toxicity.

 After completion of study treatment, patients are followed up every 4 weeks for 2 years from
 registration.
Eligibility Criteria:

 -  Histologic documentation of one of the following: breast adenocarcinoma, prostate
 adenocarcinoma or multiple myeloma

 -  At least one site of bone metastasis or bone involvement by radiologic imaging
 including plain radiograph, computed tomography (CT), positron emission tomography
 (PET) scan, PET/CT scan, magnetic resonance imaging, bone scan, or skeletal survey;
 indeterminate lesions should be confirmed by a second imaging method

 -  No prior treatment with IV bisphosphonates is allowed; prior treatment with oral
 bisphosphonates is allowed, but they must be discontinued prior to the initiation of
 protocol therapy

 -  No prior treatment with denosumab

 -  No prior treatment with radiopharmaceuticals; prior treatment with radioactive iodine
 is allowed; prostate cancer patients treated with brachytherapy are eligible

 -  Prior radiation therapy to bone is allowed, provided that at least one site of bone
 metastasis has not been irradiated and radiation is completed prior to registration;
 there should be no plan for radiation therapy to non-irradiated sites of bone
 metastases

 -  Prior adjuvant and metastatic chemotherapy, biologic therapy, and endocrine therapy is
 allowed

 -  No current treatment with investigational agent(s)

 -  Patients with known brain metastases are not eligible; patients who develop brain
 metastases during the study will be allowed to continue treatment as assigned

 -  Not pregnant and not nursing

 -  ECOG performance status 0-2

 -  Calculated creatinine clearance >= 30 mL/min

 -  Corrected serum calcium >= 8.0 mg/dL (2.00 mmol/L) and < 11.6 mg/dL (2.90 mmol/L) *
 Corrected serum calcium should be calculated using standard institutional practices