NCT00079001

Zoledronate in Preventing Skeletal (Bone)-Related Events in Men Who Are Receiving Androgen Deprivation Therapy For Prostate Cancer and Bone Metastases

Official Title:

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

Summary

RATIONALE: Zoledronate may prevent or decrease skeletal (bone)-related events (such as pain or fractures) caused by bone metastases and androgen deprivation therapy. It is not yet known whether treatment with zoledronate is effective in preventing bone-related events in patients who have prostate cancer and bone metastases.

PURPOSE: This randomized phase III trial is studying how well zoledronate works in preventing bone-related events in patients who are receiving androgen deprivation therapy for prostate cancer and bone metastases.

Eligibility

1. Histologic Documentation: Histologic documentation of prostate adenocarcinoma. Patients with small cell, neuroendocrine, or transitional cell carcinomas are not eligible.
2. Staging: At least one bone metastasis by radiographic imaging (bone scan, magnetic resonance imaging, computed tomography, or plain radiographs). Indeterminate lesions should be confirmed by a second imaging method. Imaging to document bone metastases is to be completed either within 12 weeks before registration or within 12 weeks before initiating androgen deprivation therapy for bone metastases.
3. Hormone Therapy

* While on this study, patients must receive androgen deprivation therapy (ADT) for treatment of prostate cancer. Androgen deprivation therapy may have begun prior to enrollment on this study; however patients must have initiated ADT ≤ 6 months prior to enrollment.
* Androgen deprivation therapy is defined as bilateral orchiectomy or gonadotropin- releasing hormone (GnRH) agonist with or without an antiandrogen.
* Patients treated with intermittent androgen deprivation therapy are not eligible except for patients concurrently enrolled in SWOG-9346/INT-0162/CALGB 9594, Phase III Study of Intermittent Androgen Deprivation in Patients with Stage D2 Prostate Cancer.
4. Prior Treatment:

* Hormone therapy at any point prior to 6 months before enrollment is prohibited. This includes any of the following treatments:

* orchiectomy,
* GnRH agonist (e. g., leuprolide, goserelin, triptorelin),
* estrogen therapy,
* antiandrogen (e. g., bicalutamide, flutamide, nilutamide), or
* any other therapy known to lower testosterone level or inhibit testosterone effect.
* Prior neoadjuvant and/or adjuvant hormone therapy is allowed provided that the duration of hormone therapy was six months or less and the hormone therapy was discontinued more than 6 months prior to study entry.
* No prior treatment with a bisphosphonate
* No prior treatment with denosumab
* No prior treatment with radiopharmaceuticals
* ≥ 4 weeks since completion of prior radiation therapy with at least one bone metastasis present that has NOT been radiated.
5. ECOG (CTC) performance status 0-2
6. Age: ≥ 18 years
7. Required Initial Laboratory Data:

* 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)

Disease(s) and\or Condition(s)

Metastatic Cancer

Prostate Cancer

Primary Purpose
  • TREATMENT
Intervention/Treatment
    • Type: DRUG
    • Name: zoledronic acid
    • Description: Given IV
    • Arm Group Labels: Zoledronic acid + androgen deprivation therapy
    • Type: OTHER
    • Name: placebo
    • Description: Given IV
    • Arm Group Labels: Placebo + androgen deprivation therapy
    • Type: DRUG
    • Name: androgen deprivation therapy
    • Description: Patients concurrently enrolled on the Phase III study of intermittent androgen deprivation in patients with stage D2 prostate cancer will receive androgen deprivation therapy per SWOG-9346. All other patients will receive androgen deprivation therapy at a standard dose and schedule throughout the study.
    • Arm Group Labels: Placebo + androgen deprivation therapy, Zoledronic acid + androgen deprivation therapy
    • Type: DRUG
    • Name: GnRH agonist
    • Description: Patients concurrently enrolled on the Phase III study of intermittent androgen deprivation in patients with stage D2 prostate cancer will receive the GnRH agonist per SWOG-9346. All other patients will receive GnRH agonist at a standard dose and schedule throughout the study.
    • Arm Group Labels: Placebo + androgen deprivation therapy, Zoledronic acid + androgen deprivation therapy
    • Type: DIETARY_SUPPLEMENT
    • Name: Calcium supplement
    • Description: Patients will receive 500 mg by mouth daily of a calcium supplement or a combination tablet containing approximately 500 mg elemental calcium and 400-500 IU vitamin D by mouth daily.
    • Arm Group Labels: Placebo + androgen deprivation therapy, Zoledronic acid + androgen deprivation therapy
    • Type: DIETARY_SUPPLEMENT
    • Name: Vitamin D
    • Description: Patients will receive a multivitamin tablet containing 400-500 IU vitamin D by mouth daily or a combination tablet containing approximately 500 mg elemental calcium and 400-500 IU vitamin D by mouth daily.
    • Arm Group Labels: Placebo + androgen deprivation therapy, Zoledronic acid + androgen deprivation therapy
Sponsor
  • Alliance for Clinical Trials in Oncology