RATIONALE: Androgens can stimulate the growth of prostate cancer cells. Drugs such as ketoconazole may stop the production of androgens. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether hormone therapy is more effective than combination chemotherapy in treating prostate cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of hormone therapy with that of combination chemotherapy in treating patients who have prostate cancer that has been previously treated with androgen suppression.

Condition	Treatment or Intervention	Phase
adenocarcinoma of the prostate stage III prostate cancer	Drug: docetaxel  Drug: estramustine  Drug: hydrocortisone  Drug: ketoconazole  Procedure: adrenal blockade  Procedure: chemotherapy  Procedure: endocrine therapy  Procedure: hormone therapy  Procedure: steroid therapy	Phase III

Further Study Details: 

OBJECTIVES:

• Compare time to objective progression in patients with prostate cancer and a rising prostate-specific antigen (PSA) after androgen suppression when treated with second-line hormonal therapy (ketoconazole and hydrocortisone) vs combination chemotherapy (docetaxel and estramustine).
• Compare time to PSA progression and correlate this with time to objective progression in patients treated with these regimens.
• Compare the quality of life in patients treated with these regimens.
• Compare overall survival of patients treated with these regimens.
• Compare the natural history of progression in patients treated with these regimens.
• Identify prognostic indicators of clinical outcome by immunohistochemical evaluation of apoptopic biomarkers in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior treatment with bisphosphonates (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral ketoconazole three times daily and oral hydrocortisone twice daily. Treatment continues in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive oral estramustine three times daily on days 1-5 and docetaxel IV over 1 hour on day 2. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, on day 1 of week 9, at 6 months and 1 year, and then annually for up to 10 years or until beginning of first non-protocol therapy.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.

PROJECTED ACCRUAL: A total of 590 patients (295 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 that was continuously treated with androgen suppression
• Rising prostate-specific antigen (PSA), defined as PSA > 5 ng/mL, rising on 2 consecutive measurements at least 4 weeks apart
• Gleason score 7 or higher and/or seminal vesicle involvement at diagnosis
• Patients previously treated with antiandrogen or glucocorticoid therapy must meet the following criteria:
• Must show a continued rise in PSA after stopping antiandrogen (flutamide, bicalutamide, or nilutamide) or glucocorticoid (dexamethasone or prednisone)
• At least 4 weeks continued rise in PSA after flutamide or nilutamide (6 weeks for bicalutamide)
• Testosterone less than 50 ng/dL
• Patients who have not undergone surgical castration must continue primary androgen suppression to maintain castrate levels of testosterone
• No progressive or measurable local or metastatic disease (including bone metastases)

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Granulocyte count at least 2,000/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• SGOT no greater than 2 times upper limit of normal
• Bilirubin no greater than 1.5 mg/dL

Renal:

• Creatinine no greater than 1.7 mg/dL

Cardiovascular:

• No American Heart Association class III or IV heart disease
• No uncontrolled congestive heart failure
• No life-threatening cardiac arrhythmias

Other:

• Fertile patients must use effective contraception
• No other prior malignancy unless curatively treated and disease-free for appropriate time period for specific cancer
• No preexisting peripheral neuropathy greater than grade 1
• No known hypersensitivity to polysorbate 80

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• At least 5 years since prior systemic chemotherapy

Endocrine therapy:

• See Disease Characteristics
• At least 4 weeks since prior hydrocortisone
• No prior ketoconazole

Radiotherapy:

• At least 28 days since prior radiotherapy to primary site
• No prior palliative radiotherapy
• No concurrent radiotherapy

Surgery:

• See Disease Characteristics

Other:

• Recovered form prior therapy
• At least 7 days since prior parenteral antibiotics for active infection
• No concurrent digitalis
• No concurrent H_2 blockers or proton pump inhibitors (arm I only)
• Concurrent bisphosphonates allowed provided they were initiated prior to study therapy

Alabama
      Comprehensive Cancer Institute, Huntsville,  Alabama,  35801,  United States
Arizona
      CCOP - Mayo Clinic Scottsdale Oncology Program, Scottsdale,  Arizona,  85259-5404,  United States
      Veterans Affairs Medical Center - Tucson, Tucson,  Arizona,  85723,  United States
Arkansas
      Veterans Affairs Medical Center - Little Rock, Little Rock,  Arkansas,  72205,  United States
California
      Cedars-Sinai Comprehensive Cancer Center at Cedars-Sinai Medical Center, Los Angeles,  California,  90048,  United States
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010-3000,  United States
      Naval Medical Center - San Diego, San Diego,  California,  92134-3202,  United States
      Rebecca and John Moores UCSD Cancer Center, La Jolla,  California,  92093-0658,  United States
      UCSF Comprehensive Cancer Center, San Francisco,  California,  94115,  United States
      Veterans Affairs Outpatient Clinic - Martinez, Martinez,  California,  94553,  United States
Colorado
      Boulder Community Hospital, Boulder,  Colorado,  80301-9019,  United States
      CCOP - Colorado Cancer Research Program, Incorporated, Denver,  Colorado,  80224,  United States
      Hope Cancer Care Center at Longmont United Hospital, Longmont,  Colorado,  80501,  United States
      Medical Center of Aurora - South Campus, Aurora,  Colorado,  80012-0000,  United States
      Penrose Cancer Center at Penrose Hospital, Colorado Springs,  Colorado,  80933,  United States
      Porter Adventist Hospital, Denver,  Colorado,  80210,  United States
      Presbyterian - St. Luke's Medical Center, Denver,  Colorado,  80218,  United States
      Rocky Mountain Cancer Centers - Denver Rose, Denver,  Colorado,  80220,  United States
      Rocky Mountain Cancer Centers - Thornton, Thornton,  Colorado,  80221,  United States
      Sky Ridge Medical Center, Lone Tree,  Colorado,  80124,  United States
      St. Joseph Hospital, Denver,  Colorado,  80218-1191,  United States
      St. Mary-Corwin Regional Medical Center, Pueblo,  Colorado,  81004,  United States
      Swedish Medical Center, Englewood,  Colorado,  80112,  United States
      Veterans Affairs Medical Center - Denver, Denver,  Colorado,  80220,  United States
District of Columbia
      Walter Reed Army Medical Center, Washington,  District of Columbia,  20307-5001,  United States
Florida
      H. Lee Moffitt Cancer Center and Research Institute at University of South Florida, Tampa,  Florida,  33612-9497,  United States
      Memorial Regional Cancer Center at Memorial Regional Hospital, Hollywood,  Florida,  33021,  United States
      Veterans Affairs Medical Center - Tampa (Haley), Tampa,  Florida,  33612,  United States
Georgia
      Veterans Affairs Medical Center - Atlanta (Decatur), Decatur,  Georgia,  30033,  United States
Hawaii
      MBCCOP - Hawaii, Honolulu,  Hawaii,  96813,  United States
Illinois
      CCOP - Carle Cancer Center, Urbana,  Illinois,  61801,  United States
      CCOP - Central Illinois, Decatur,  Illinois,  62526,  United States
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61615-7828,  United States
      Decatur Memorial Hospital Cancer Care Institute, Decatur,  Illinois,  62526,  United States
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States
      Veterans Affairs Medical Center - Hines, Hines,  Illinois,  60141,  United States
      West Suburban Center for Cancer Care, River Forest,  Illinois,  60305,  United States
Indiana
      Indiana University Cancer Center, Indianapolis,  Indiana,  46202-5289,  United States
      Veterans Affairs Medical Center - Indianapolis (Roudebush), Indianapolis,  Indiana,  46202,  United States
Iowa
      CCOP - Cedar Rapids Oncology Project, Cedar Rapids,  Iowa,  52403-1206,  United States
Kansas
      Veterans Affairs Medical Center - Wichita, Wichita,  Kansas,  67218,  United States
Kentucky
      Veterans Affairs Medical Center - Lexington, Lexington,  Kentucky,  40502-2236,  United States
Louisiana
      CCOP - Ochsner, New Orleans,  Louisiana,  70121,  United States
      MBCCOP - LSU Health Sciences Center, New Orleans,  Louisiana,  70112,  United States
      Veterans Affairs Medical Center - New Orleans, New Orleans,  Louisiana,  70112,  United States
      Veterans Affairs Medical Center - Shreveport, Shreveport,  Louisiana,  71101-4295,  United States
Maryland
      Greenebaum Cancer Center at University of Maryland Medical Center, Baltimore,  Maryland,  21201,  United States
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231,  United States
Michigan
      CCOP - Kalamazoo, Kalamazoo,  Michigan,  49007-3731,  United States
      Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph, Saint Joseph,  Michigan,  49085,  United States
      Veterans Affairs Medical Center - Detroit, Detroit,  Michigan,  48201-1932,  United States
      West Michigan Cancer Center, Kalamazoo,  Michigan,  49007,  United States
Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States
Mississippi
      Veterans Affairs Medical Center - Jackson, Jackson,  Mississippi,  39216,  United States
Missouri
      CCOP - Kansas City, Kansas City,  Missouri,  64131,  United States
      Ellis Fischel Cancer Center at University of Missouri - Columbia, Columbia,  Missouri,  65203,  United States
      Missouri Baptist Cancer Center, Saint Louis,  Missouri,  63131,  United States
Nevada
      CCOP - Southern Nevada Cancer Research Foundation, Las Vegas,  Nevada,  89106,  United States
New Hampshire
      New Hampshire Oncology-Hematology, PA - Hooksett, Hooksett,  New Hampshire,  03106,  United States
      Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, Lebanon,  New Hampshire,  03756-0002,  United States
New Jersey
      Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School, New Brunswick,  New Jersey,  08903,  United States
New Mexico
      MBCCOP - University of New Mexico HSC, Albuquerque,  New Mexico,  87131,  United States
      Veterans Affairs Medical Center - Albuquerque, Albuquerque,  New Mexico,  87108-5138,  United States
New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States
      Mount Sinai Medical Center, New York,  New York,  10029,  United States
      NYU School of Medicine's Kaplan Comprehensive Cancer Center, New York,  New York,  10016,  United States
      Roswell Park Cancer Institute, Buffalo,  New York,  14263-0001,  United States
      Veterans Affairs Medical Center - Syracuse, Syracuse,  New York,  13210,  United States
North Carolina
      Cape Fear Valley Health System, Fayetteville,  North Carolina,  28302-2000,  United States
      CCOP - Southeast Cancer Control Consortium, Goldsboro,  North Carolina,  27534-9479,  United States
Ohio
      Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University, Columbus,  Ohio,  43210-1240,  United States
      CCOP - Columbus, Columbus,  Ohio,  43206,  United States
      CCOP - Toledo Community Hospital, Toledo,  Ohio,  43623-3456,  United States
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195,  United States
      Veterans Affairs Medical Center - Cincinnati, Cincinnati,  Ohio,  45220-2288,  United States
      Veterans Affairs Medical Center - Dayton, Dayton,  Ohio,  45428-1002,  United States
Oklahoma
      Oklahoma University Medical Center, Oklahoma City,  Oklahoma,  73104,  United States
Oregon
      Veterans Affairs Medical Center - Portland, Portland,  Oregon,  97207,  United States
Pennsylvania
      Abramson Cancer Center at the University of Pennsylvania, Philadelphia,  Pennsylvania,  19104,  United States
      CCOP - Geisinger Clinic and Medical Center, Danville,  Pennsylvania,  17822-2001,  United States
      Fox Chase Cancer Center, Philadelphia,  Pennsylvania,  19111-2497,  United States
      Western Pennsylvania Hospital, Pittsburgh,  Pennsylvania,  15224,  United States
South Carolina
      Veterans Affairs Medical Center - Charleston, Charleston,  South Carolina,  29401-5799,  United States
South Dakota
      CCOP - Sioux Community Cancer Consortium, Sioux Falls,  South Dakota,  57104,  United States
Tennessee
      Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center, Nashville,  Tennessee,  37232-6307,  United States
Texas
      CCOP - Scott and White Hospital, Temple,  Texas,  76508,  United States
      Harrington Cancer Center, Amarillo,  Texas,  79106,  United States
      Veterans Affairs Medical Center - Amarillo, Amarillo,  Texas,  79106,  United States
      Veterans Affairs Medical Center - San Antonio (Murphy), San Antonio,  Texas,  78229,  United States
      Veterans Affairs Medical Center - Temple, Temple,  Texas,  76504,  United States
Utah
      Veterans Affairs Medical Center - Salt Lake City, Salt Lake City,  Utah,  84148,  United States
Virginia
      Martha Jefferson Hospital, Charlottesville,  Virginia,  22902,  United States
      Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke, Roanoke,  Virginia,  24014,  United States
Washington
      Veterans Affairs Medical Center - Seattle, Seattle,  Washington,  98108,  United States
West Virginia
      St. Mary's Medical Center, Huntington,  West Virginia,  25701,  United States
Wisconsin
      CCOP - St. Vincent Hospital Cancer Center, Green Bay, Green Bay,  Wisconsin,  54307-3453,  United States
      Medical College of Wisconsin Cancer Center, Milwaukee,  Wisconsin,  53226-3596,  United States
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-0001,  United States

Study chairs or principal investigators

Michael A. Carducci, MD,  Study Chair,  Sidney Kimmel Cancer Center   
Nirmala Bhoopalam, MD,  Study Chair,  Veterans Affairs Medical Center - Hines   
Gregory P. Swanson, MD,  Deaconess Medical Center   
William Dahut, MD,  Study Chair,  National Cancer Institute (NCI)   

Study ID Numbers:  CDR0000069088; ECOG-E1899; ECOG-1899; SWOG-E1899; CALGB-E1899; NCT00027859
Record last reviewed:  February 2005
Last Updated:  February 8, 2005
Record first received:  December 7, 2001
ClinicalTrials.gov Identifier:  NCT00027859
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08