A Randomized Double-Blind, Placebo-Controlled Phase III Study of Early Versus Standard Zoledronic Acid to Prevent Skeletal Related Events in Men With Prostate Cancer Metastatic to Bone

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed adenocarcinoma of the prostate

- No small cell, neuroendocrine, or transitional cell carcinomas

- At least 1 bone metastasis by bone scan, MRI, CT scan, or plain radiographs

- Indeterminate lesions should be confirmed by a second imaging method

- At least 1 bone metastasis with no prior irradiation

- Concurrent androgen deprivation therapy required, defined as any of the following:

- Bilateral orchiectomy

- Gonadotropin-releasing hormone (GnRH) agonist with or without an antiandrogen

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- ECOG 0-2

Life expectancy

- Not specified

Hematopoietic

- Not specified

Hepatic

- Not specified

Renal

- Creatinine clearance ≥ 30 mL/min

- Corrected calcium ≥ 8.0 mg/dL and < 11.6 mg/dL

Other

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Concurrent standard biologic response modifiers allowed during open-label therapy
only

Chemotherapy

- Concurrent standard cytotoxic chemotherapy allowed during open-label therapy only

Endocrine therapy

- See Disease Characteristics

- Prior neoadjuvant and/or adjuvant hormonal therapy allowed provided duration of
therapy was no more than 6 months AND therapy was discontinued more than 6 months
before study entry

- No more than 6 months since initiation of any of the following hormonal therapies:

- Orchiectomy

- GnRH agonist (e.g., leuprolide, goserelin, or triptorelin)

- Estrogen therapy

- Antiandrogens (e.g., bicalutamide, flutamide, or nilutamide)

- Any other therapy known to lower testosterone levels or inhibit testosterone
effect

- No intermittent androgen deprivation therapy except for patients concurrently
enrolled on SWOG-9346

- Concurrent palliative corticosteroids allowed during open-label therapy only

- Concurrent standard hormonal agents allowed during open-label therapy only

Radiotherapy

- See Disease Characteristics

- No prior radiopharmaceuticals

- At least 4 weeks since prior radiotherapy

- Concurrent standard radiotherapy to extraskeletal tumor sites allowed during
open-label therapy only

Surgery

- See Disease Characteristics

Other

- No prior bisphosphonates

- No prior denosumab

- No other concurrent agents expected to alter osteoclast activity (e.g., denosumab,
calcitonin, mithramycin, gallium nitrate, or any other bisphosphonate)

- Concurrent daily supplemental elemental calcium (500 mg) and a multivitamin
containing cholecalciferol (Vitamin D) (400 IU) OR a combination tablet containing
both recommended

- Concurrent standard marketed antineoplastic therapies allowed during open-label
therapy only