Zoledronic Acid in Treating Patients With Metastatic Breast Cancer, Metastatic Prostate Cancer, or Multiple Myeloma With Bone Involvement

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