RATIONALE: Androgens can stimulate the growth of prostate cancer cells. Drugs such as goserelin and leuprolide may fight prostate cancer by stopping the adrenal glands from producing androgens. Drugs used in chemotherapy such as doxorubicin work in different ways to stop tumor cells from dividing so they stop growing or die. Zoledronate may prevent bone loss and stop the growth of tumor cells in bone. Radioactive substances such as strontium-89 may relieve bone pain associated with prostate cancer. It is not yet known whether hormone (androgen) ablation therapy and chemotherapy combined with zoledronate is more effective with or without strontium-89 in treating prostate cancer and bone metastases.

PURPOSE: This randomized phase II trial is studying giving hormone ablation therapy, doxorubicin, and zoledronate together with strontium-89 to see how well it works compared to hormone ablation therapy, doxorubicin, and zoledronate alone in treating patients with androgen-dependent prostate cancer and bone metastases.

Condition	Treatment or Intervention	Phase
recurrent prostate cancer stage IV prostate cancer bone metastases	Drug: doxorubicin  Drug: goserelin  Drug: leuprolide  Drug: strontium chloride Sr 89  Drug: zoledronate  Procedure: ablative endocrine surgery  Procedure: bone metastases prevention  Procedure: chemotherapy  Procedure: endocrine therapy  Procedure: hormone therapy  Procedure: isotope therapy  Procedure: orchiectomy  Procedure: radiation therapy  Procedure: releasing factor agonist therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Compare the clinical efficacy of hormonal ablative therapy combined with doxorubicin and zoledronate with or without strontium chloride Sr 89, in terms of progression-free survival, in patients with androgen-dependent prostate cancer and bone metastases.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to the number of bony metastases (≤ 6 vs > 6). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive hormonal ablative therapy comprising luteinizing hormone-releasing hormone agonist (e.g., leuprolide or goserelin) continuously during study treatment OR bilateral orchiectomy. Patients also receive doxorubicin IV on days 1, 8, and 15 every 28 days for 2 courses; zoledronate IV over 15 minutes on day 1 every 28 days for 6 courses; and a single dose of strontium chloride Sr 89 IV over 1-2 minutes on day 1.
• Arm II: Patients receive hormonal ablative therapy, doxorubicin, and zoledronate as in arm I. In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 80 patients (40 per treatment arm) will be accrued for this study within 20 months.

Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed prostate cancer
• Osteoblastic metastases on bone scan or CT scan
• Androgen-dependent disease
• Previously treated with neoadjuvant or intermittent hormonal ablative therapy* at least 3 years ago AND has reinitiated hormonal ablative therapy within 3 months before study entry NOTE: *Therapy was less than 3 years in duration
• No symptomatic bulky lymphadenopathy causing scrotal or pedal edema
• No significant local invasive disease with bladder invasion
• No evidence or suspicion of myelodysplastic syndromes by complete blood count and bone marrow biopsy
• No small cell carcinoma, purely lytic bone metastasis, or bulky (i.e., ≥ 5 cm) visceral or nodal disease in the absence of bone involvement by biopsy
• No known brain metastases

PATIENT CHARACTERISTICS: Age

• Not specified

Performance status

• ECOG 0-3 OR
• Karnofsky 40-100%

Life expectancy

• More than 3 months

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• WBC ≥ 3,000/mm^3

Hepatic

• AST and ALT ≤ 2.5 times upper limit of normal
• Bilirubin normal

Renal

• Creatinine ≤ 3.0 mg/dL
• Calcium level ≥ 8 mg/dL

Cardiovascular

• LVEF ≥ 45%
• No history of congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• Fertile patients must use effective contraception
• No prior allergic reaction attributed to compounds of similar chemical or biological composition to zoledronate or other study drugs
• No other malignancy within the past 5 years except nonmelanoma skin cancer
• No active or ongoing infection
• No psychiatric illness or social situation that would preclude study compliance
• No untreated symptomatic spinal cord compressions
• No other concurrent uncontrolled illness

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• Prior doxorubicin allowed provided the cumulative dosage was ≤ 250 mg/m^2
• No more than 1 prior chemotherapy regimen

Endocrine therapy

• See Disease Characteristics

Radiotherapy

• No prior strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium

Surgery

• Not specified

Other

• Prior zoledronate allowed provided treatment was no more than 3 months in duration
• Other prior bisphosphonates allowed
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational agents
• No other concurrent anticancer therapy

Alabama
      MBCCOP - Gulf Coast, Mobile,  Alabama,  36607,  United States; Recruiting
Arkansas
      Cooper Clinic, P.A., Fort Smith,  Arkansas,  72913,  United States; Recruiting
California
      CCOP - Santa Rosa Memorial Hospital, Santa Rosa,  California,  95403,  United States; Recruiting
Delaware
      CCOP - Christiana Care Health Services, Newark,  Delaware,  19713,  United States; Recruiting
Georgia
      Atlanta Cancer Care - Perimeter (Lake Hearn), Atlanta,  Georgia,  30342,  United States; Recruiting
Illinois
      CCOP - Carle Cancer Center, Urbana,  Illinois,  61801,  United States; Recruiting
      CCOP - Central Illinois, Decatur,  Illinois,  62526,  United States; Recruiting
      MBCCOP - University of Illinois at Chicago, Chicago,  Illinois,  60612-7323,  United States; Recruiting
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States; Recruiting
Michigan
      CCOP - Grand Rapids, Grand Rapids,  Michigan,  49503,  United States; Recruiting
      CCOP - Kalamazoo, Kalamazoo,  Michigan,  49007-3731,  United States; Recruiting
      CCOP - Michigan Cancer Research Consortium, Ann Arbor,  Michigan,  48106,  United States; Recruiting
Minnesota
      CCOP - Metro-Minnesota, Saint Louis Park,  Minnesota,  55416,  United States; Recruiting
Missouri
      CCOP - Cancer Research for the Ozarks, Springfield,  Missouri,  65807,  United States; Recruiting
      CCOP - Kansas City, Kansas City,  Missouri,  64131,  United States; Recruiting
Nebraska
      CCOP - Missouri Valley Cancer Consortium, Omaha,  Nebraska,  68106,  United States; Recruiting
Nevada
      CCOP - Southern Nevada Cancer Research Foundation, Las Vegas,  Nevada,  89106,  United States; Recruiting
New York
      CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C., East Syracuse,  New York,  13057,  United States; Recruiting
Ohio
      CCOP - Columbus, Columbus,  Ohio,  43206,  United States; Recruiting
      CCOP - Dayton, Dayton,  Ohio,  45429,  United States; Recruiting
Oklahoma
      Oklahoma Oncology, Inc. - Saint Francis Campus, Tulsa,  Oklahoma,  74136,  United States; Recruiting
Oregon
      CCOP - Columbia River Oncology Program, Portland,  Oregon,  97225,  United States; Recruiting
Pennsylvania
      CCOP - MainLine Health, Wynnewood,  Pennsylvania,  19096,  United States; Recruiting
South Carolina
      CCOP - Greenville, Greenville,  South Carolina,  29615,  United States; Recruiting
      CCOP - Upstate Carolina, Spartanburg,  South Carolina,  29303,  United States; Recruiting
Texas
      CCOP - Scott and White Hospital, Temple,  Texas,  76508,  United States; Recruiting
      MD Anderson Cancer Center at University of Texas, Houston,  Texas,  77030-4009,  United States; Recruiting
Virginia
      Cancer Outreach Associates - Abingdon, Abingdon,  Virginia,  24211,  United States; Recruiting
Washington
      CCOP - Northwest, Tacoma,  Washington,  98405-0986,  United States; Recruiting
      CCOP - Virginia Mason Research Center, Seattle,  Washington,  98101,  United States; Recruiting
Wisconsin
      CCOP - Marshfield Clinic Research Foundation, Marshfield,  Wisconsin,  54449,  United States; Recruiting
Puerto Rico
      MBCCOP - San Juan, San Juan,  00921-3201,  Puerto Rico; Recruiting

Study chairs or principal investigators

Shi-Ming Tu, MD,  Study Chair,  M.D. Anderson Cancer Center   

Study ID Numbers:  CDR0000360625; MDA-2003-0922; NCI-6459; NCT00081159
Record last reviewed:  November 2004
Last Updated:  April 4, 2005
Record first received:  April 7, 2004
ClinicalTrials.gov Identifier:  NCT00081159
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08