Zoledronate in Preventing Skeletal (Bone)-Related Events in Men Who Are Receiving Androgen Deprivation Therapy For Prostate Cancer and Bone Metastases
Condition: Metastatic Cancer; Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: zoledronic acid; placebo; androgen deprivation therapy; GnRH agonist; Calcium supplement; Vitamin D
Intervention description: Given IV; Given IV; 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.; 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.; 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.; 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.
Intervention MeSH terms: Vitamin D; Zoledronic Acid; Calcium; Androgens
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 645.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: adenocarcinoma of the prostate; recurrent prostate cancer; stage IV prostate cancer; bone metastases

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 criteria:

        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)