RATIONALE: Androgens can stimulate the growth of prostate cancer cells. Drugs such as luteinizing hormone-releasing hormone agonist, flutamide, and bicalutamide may stop the adrenal glands from producing androgens. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Combining hormone therapy with chemotherapy may kill more tumor cells. It is not yet known whether chemotherapy given at the same time as hormone therapy is more effective than chemotherapy given after hormone therapy in treating prostate cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy given at the same time as hormone therapy with that of chemotherapy given after hormone therapy in treating patients who have prostate cancer.

Condition	Treatment or Intervention	Phase
adenocarcinoma of the prostate stage II prostate cancer stage III prostate cancer stage IV prostate cancer recurrent prostate cancer	Drug: bicalutamide  Drug: docetaxel  Drug: doxorubicin  Drug: estramustine  Drug: flutamide  Drug: ketoconazole  Drug: paclitaxel  Drug: vinblastine  Procedure: antiandrogen therapy  Procedure: chemotherapy  Procedure: endocrine therapy  Procedure: hormone therapy  Procedure: releasing factor agonist therapy	Phase III

Further Study Details: 

OBJECTIVES: Primary

• Compare the survival of patients with high-risk hormone-naive prostate cancer treated with androgen blockade with concurrent chemotherapy vs delayed chemotherapy.

Secondary

• Compare biochemical control in patients treated with these regimens.
• Determine the toxicity of these regimens in these patients.
• Compare the time to clinical failure, as measured by progression on bone scan or CT scan or a prostate-specific antigen doubling time of ≤ 32 weeks, in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior therapy (surgery vs radiotherapy and/or brachytherapy vs both), original combined Gleason score (6 vs 7 vs 8-10), and prior vaccine therapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Patients receive androgen blockade (AB) comprising a luteinizing-hormone releasing-hormone agonist continuously and oral flutamide or oral bicalutamide once daily for at least 1 month. Within 4 weeks of initiation of AB, patients begin chemotherapy. Patients receive 1, and only 1, of the following chemotherapy regimens:
• Regimen A: Patients receive oral estramustine 3 times daily on days 1-5 and docetaxel IV on day 3. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
• Regimen B: Patients receive oral estramustine 3 times daily on days 1-5 and paclitaxel IV on days 3, 10, 17, 24, 31, and 38. Treatment repeats every 56 days for 4 courses in the absence of disease progression or unacceptable toxicity.
• Regimen C: Patients receive oral ketoconazole 3 times daily on days 1-7, 15-21, and 29-35; doxorubicin IV on days 1, 15, and 29; vinblastine IV on days 8, 22, and 36; and oral estramustine 3 times daily on days 8-14, 22-28, and 36-42. Treatment repeats every 56 days for 4 courses in the absence of disease progression or unacceptable toxicity.
• Regimen D: Patients receive oral estramustine 3 times daily on days 1-4 and docetaxel IV over 1 hour on days 3, 10, and 17. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
• Regimen E: Patients receive docetaxel IV on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
• Regimen F: Patients receive docetaxel IV on days 1, 8, and 15. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
• Regimen G: With approval from the protocol chair, patients may receive a regimen that has been demonstrated in a published phase II study to have at least a 50% response rate as measured by PSA decrease from baseline over 2 measurements 28 days apart or a decrease in measurable soft tissue disease by 50% in 2 dimensions.
• Arm II: Patients receive AB as in arm I. Patients continue with AB until clinical failure, at which time patients receive chemotherapy as in arm I. Patients who have a response may continue to receive chemotherapy beyond 4 courses. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 1,050 patients will be accrued for this study within 4-6 years.

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

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of adenocarcinoma of the prostate
• Failed local treatments (surgery and/or radiotherapy and/or brachytherapy) as defined by a rising prostate-specific antigen level of at least 2.0 ng/mL (confirmed by 2 measurements at least 2 weeks apart) and a doubling time of 32 weeks or less
• No clinical or radiographic evidence of disease
• Original Gleason score of at least 7 OR Gleason score of 6 with capsular penetration or positive seminal vesicles or lymph nodes
• No metastases

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• Zubrod 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Absolute granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 10 g/dL
• No history of bleeding disorders that would contraindicate warfarin, including clotting factor defects

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• AST/ALT no greater than 1.5 times upper limit of normal

Renal:

• Creatinine no greater than 1.5 mg/dL
• BUN no greater than 1.2 times normal

Cardiovascular:

• No symptomatic heart disease
• No history of myocardial infarction
• No history of thromboembolic events (e.g., deep vein thrombosis, symptomatic cerebrovascular events, or pulmonary embolism)

Other:

• No other major medical or psychiatric illness that would preclude study entry
• No other prior or concurrent invasive malignancy within the past 5 years except superficial skin cancer
• No history of esophageal varices
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy:

• At least 6 weeks since prior vaccine therapy

Chemotherapy:

• At least 5 years since prior chemotherapy

Endocrine therapy:

• Prior adjuvant or neoadjuvant hormonal therapy of less than 8 months duration allowed
• At least 1 year since prior androgen therapy

Radiotherapy:

• See Disease Characteristics
• At least 5 years since prior radiotherapy to sites other than prostate

Surgery:

• See Disease Characteristics

Other:

• Concurrent warfarin allowed
• Concurrent bisphosphonate therapy initiated prior to or after randomization allowed

Arizona
      Foundation for Cancer Research and Education, Phoenix,  Arizona,  85013,  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
      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
      Memorial Hospital Cancer Center, Colorado Springs,  Colorado,  80909,  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
Florida
      Gulf Coast Cancer Treatment Center, Panama City,  Florida,  32405-4587,  United States
      Shands Cancer Center at the University of Florida Health Science Center, Gainesville,  Florida,  32610-0385,  United States
      Tallahassee Memorial Hospital, Tallahassee,  Florida,  32308,  United States
      University of Miami Sylvester Comprehensive Cancer Center, Miami,  Florida,  33136,  United States
      Veterans Affairs Medical Center - Tampa (Haley), Tampa,  Florida,  33612,  United States
Idaho
      Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center, Boise,  Idaho,  83706,  United States
Illinois
      Veterans Affairs Medical Center - Hines, Hines,  Illinois,  60141,  United States
Iowa
      John Stoddard Cancer Center at Iowa Lutheran Hospital, Des Moines,  Iowa,  50316-2301,  United States
      John Stoddard Cancer Center at Iowa Methodist Medical Center, Des Moines,  Iowa,  50309,  United States
      Mercy Cancer Center at Mercy Medical Center - Des Moines, Des Moines,  Iowa,  50314,  United States
      Wendt Regional Cancer Center at Finley Hospital, Dubuque,  Iowa,  52001,  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
      Veterans Affairs Medical Center - New Orleans, New Orleans,  Louisiana,  70112,  United States
      Veterans Affairs Medical Center - Shreveport, Shreveport,  Louisiana,  71101-4295,  United States
Maryland
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231,  United States
Michigan
      University of Michigan Comprehensive Cancer Center, Ann Arbor,  Michigan,  48109-0010,  United States
      Veterans Affairs Medical Center - Detroit, Detroit,  Michigan,  48201-1932,  United States
      West Michigan Cancer Center, Kalamazoo,  Michigan,  49007,  United States
Mississippi
      Veterans Affairs Medical Center - Jackson, Jackson,  Mississippi,  39216,  United States
Missouri
      Cancer Research for the Ozarks, Springfield,  Missouri,  65807,  United States
Nebraska
      Midlands Cancer Center at Midlands Community Hospital, Papillion,  Nebraska,  68128-4157,  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
      Lipson Cancer and Blood Center at Rochester General Hospital, Rochester,  New York,  14621,  United States
      NYU School of Medicine's Kaplan Comprehensive Cancer Center, New York,  New York,  10016,  United States
North Carolina
      CCOP - Southeast Cancer Control Consortium, Goldsboro,  North Carolina,  27534-9479,  United States
Ohio
      Akron City Hospital at Summa Health System, Akron,  Ohio,  44304,  United States
      Akron General's McDowell Cancer Center, Akron,  Ohio,  44302,  United States
      Cancer Care Center, Incorporated, Salem,  Ohio,  44460,  United States
      Cancer Treatment Center, Wooster,  Ohio,  44691,  United States
      Veterans Affairs Medical Center - Cincinnati, Cincinnati,  Ohio,  45220-2288,  United States
      Veterans Affairs Medical Center - Dayton, Dayton,  Ohio,  45428-1002,  United States
Oregon
      Veterans Affairs Medical Center - Portland, Portland,  Oregon,  97207,  United States
Pennsylvania
      Fox Chase Cancer Center, Philadelphia,  Pennsylvania,  19111,  United States
      Mercy Fitzgerald Hospital, Darby,  Pennsylvania,  19023,  United States
      Mercy Hospital Cancer Center - Scranton, Scranton,  Pennsylvania,  18501,  United States
      Penn State Cancer Institute at Milton S. Hershey Medical Center, Hershey,  Pennsylvania,  17033-0850,  United States
South Carolina
      CCOP - Greenville, Greenville,  South Carolina,  29615,  United States
      Veterans Affairs Medical Center - Charleston, Charleston,  South Carolina,  29401-5799,  United States
South Dakota
      Rapid City Regional Hospital, Rapid City,  South Dakota,  57709,  United States
Tennessee
      Erlanger Cancer Center, Chattanooga,  Tennessee,  37403,  United States
      Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center, Nashville,  Tennessee,  37232-5671,  United States
      Veterans Affairs Medical Center - Memphis, Memphis,  Tennessee,  38104,  United States
Texas
      University of Texas Medical Branch, Galveston,  Texas,  77555-0209,  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
      Cottonwood Hospital Medical Center, Murray,  Utah,  84107,  United States
      Dixie Regional Medical Center, Saint George,  Utah,  84770,  United States
      McKay-Dee Hospital Center, Ogden,  Utah,  84403,  United States
      Utah Valley Regional Medical Center - Provo, Provo,  Utah,  84604,  United States
      Veterans Affairs Medical Center - Salt Lake City, Salt Lake City,  Utah,  84148,  United States
Washington
      Veterans Affairs Medical Center - Seattle, Seattle,  Washington,  98108,  United States
Wisconsin
      All Saints Cancer Center at All Saints Healthcare, Racine,  Wisconsin,  53405,  United States
      CCOP - Marshfield Clinic Research Foundation, Marshfield,  Wisconsin,  54449,  United States
      CCOP - St. Vincent Hospital Cancer Center, Green Bay, Green Bay,  Wisconsin,  54301,  United States
Australia, New South Wales
      Westmead Hospital, Westmead,  New South Wales,  2145,  Australia
Peru
      Instituto de Enfermedades Neoplasicas, Lima,  34,  Peru
Puerto Rico
      San Juan City Hospital, San Juan,  00936-7344,  Puerto Rico

Study chairs or principal investigators

Kenneth James Pienta, MD, FACP,  Study Chair,  University of Michigan Comprehensive Cancer Center   
Naomi S. Balzer-Haas, MD,  Study Chair,  Fox Chase Cancer Center   
Arif Hussain, MD,  Study Chair,  University of Maryland Greenebaum Cancer Center   
Gregory P. Swanson, MD,  Study Chair,  Deaconess Medical Center   
Primo N. Lara, MD,  University of California Davis Cancer Center   

Study ID Numbers:  CDR0000069186; RTOG-P-0014; CTSU; RTOG-DEV-1028; ECOG-RTOG-P-0014; CALGB-RTOG-P-0014; SWOG-RTOG-P-0014; NCT00030654
Record last reviewed:  February 2005
Last Updated:  February 17, 2005
Record first received:  February 14, 2002
ClinicalTrials.gov Identifier:  NCT00030654
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08