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.

Condition	Treatment or Intervention	Phase
adenocarcinoma of the prostate recurrent prostate cancer stage IV prostate cancer bone metastases	Drug: zoledronate  Procedure: bone metastases prevention	Phase III

Further Study Details: 

OBJECTIVES: Primary

• Compare the time to first skeletal-related events in patients with prostate cancer and bone metastases undergoing androgen deprivation therapy when treated with zoledronate vs placebo.

Secondary

• Compare the incidence of vertebral fractures at 2 years in patients treated with these regimens.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study followed by an open-label study. Patients are stratified according to ECOG performance status (0-1 vs 2), prior skeletal-related event (no vs yes), and serum alkaline phosphatase (< upper limit of normal [ULN] vs ≥ ULN). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive zoledronate IV over 15 minutes on day 1.
• Arm II: Patients receive placebo IV over 15 minutes on day 1. In both arms, courses repeat every 4 weeks in the absence of disease progression or a skeletal-related event. All patients receive concurrent androgen deprivation therapy. Patients also receive oral calcium and cholecalciferol (vitamin D) supplements daily.

Patients progressing to androgen-independent prostate cancer proceed to open-label therapy comprising zoledronate IV over 15 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or a skeletal-related event.

Patients are followed for at least 3 years.

PROJECTED ACCRUAL: A total of 680 patients (340 per treatment arm) will be accrued for this study within 4 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

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 ≤ 3.0 mg/dL
• 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 1 year before study entry
• No more than 3 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 and/or skeletal tumor sites allowed during open-label therapy only

Surgery

• See Disease Characteristics

Other

• No prior bisphosphonates
• No other concurrent agents expected to alter osteoclast activity (e.g., calcitonin, mithramycin, gallium nitrate, or any other bisphosphonate)
• Concurrent standard marketed antineoplastic therapies allowed during open-label therapy only

Arkansas
      Arkansas Cancer Research Center at University of Arkansas for Medical Sciences, Little Rock,  Arkansas,  72205,  United States; Recruiting
California
      Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angeles,  California,  90048,  United States; Recruiting
      UCSF Comprehensive Cancer Center, San Francisco,  California,  94115,  United States; Recruiting
Illinois
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States; Recruiting
Massachusetts
      Beth Israel Deaconess Medical Center, Boston,  Massachusetts,  02215,  United States; Recruiting
New York
      Mount Sinai Medical Center, New York,  New York,  10029,  United States; Recruiting

Study chairs or principal investigators

Matthew R. Smith, MD,  Study Chair,  Massachusetts General Hospital   
Rajesh Valchand Shah, MD,  Study Chair,  Arkansas Cancer Research Center at University of Arkansas for Medical Sciences   

Study ID Numbers:  CDR0000353209; CALGB-90202; ECOG-90202; NCT00079001; SWOG-CALGB-90202
Record last reviewed:  November 2004
Last Updated:  March 10, 2005
Record first received:  March 8, 2004
ClinicalTrials.gov Identifier:  NCT00079001
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08