RATIONALE: Androgens can stimulate the growth of prostate cancer cells. Estramustine may fight prostate cancer by reducing the production of androgens. Exisulind may stop the growth of prostate cancer by stopping blood flow to the tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining these therapies may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining estramustine with exisulind and docetaxel in treating patients who have metastatic prostate cancer that has not responded to hormone therapy.

Condition	Treatment or Intervention	Phase
adenocarcinoma of the prostate recurrent prostate cancer stage IV prostate cancer	Drug: docetaxel  Drug: estramustine  Drug: exisulind  Procedure: chemotherapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the time to objective and biochemical progression and response proportion (objective and post-therapy changes in PSA) in patients with hormone refractory metastatic prostate cancer treated with docetaxel, estramustine, and exisulind.
• Determine the toxic effects of this regimen in these patients.
• Determine the overall survival of patients treated with this regimen.

OUTLINE: Patients receive oral estramustine 3 times daily on days 1-5, docetaxel IV over 1 hour on day 2, and oral exisulind twice daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years.

PROJECTED ACCRUAL: A total of 72 patients will be accrued for this study within 18 months.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate
• Progressive systemic (metastatic) disease despite castrate levels of testosterone secondary to orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonist therapy
• Castrate levels of testosterone must be maintained
• LHRH analog therapy should be continued
• Failed prior standard androgen-deprivation therapy
• Serum testosterone no greater than 50 ng/mL for patients who have not had bilateral orchiectomy
• Evidence of metastatic disease on CT scan, MRI, or bone scan (no positron-emission tomography or prostascint)
• Evidence of progressive disease after most recent prior therapy (including hormonal therapy) as defined by 1 of the following:
• Measurable disease progression
• More than 20% increase in the sum of the longest diameters of target lesions from the time of maximal regression or the appearance of 1 or more new lesions
• Bone scan progression
• Appearance of 1 or more new lesions on bone scan attributable to prostate cancer AND
• PSA at least 5 ng/mL
• PSA progression
• PSA at least 5 ng/mL which has increased serially from baseline on 2 occasions (at least 1 week apart) NOTE: If the confirmatory PSA is less than screening PSA, an additional test for rising PSA is required

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• AST and ALT no greater than 1.5 times upper limit of normal (ULN)
• Bilirubin no greater than ULN

Renal

• Creatinine no greater than 1.5 times ULN

Cardiovascular

• No myocardial infarction within the past year
• No significant change in anginal pattern within the past year
• No congestive heart failure
• No New York Heart Association class II-IV heart disease
• No deep vein thrombosis within the past year

Pulmonary

• No pulmonary embolus within the past year

Other

• No clinically significant peripheral neuropathy
• No known hypersensitivity to sulindac
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• No prior cytotoxic chemotherapy (including estramustine or suramin)
• No other concurrent chemotherapy

Endocrine therapy

• See Disease Characteristics
• At least 4 weeks since prior flutamide and megestrol
• At least 6 weeks since prior bicalutamide and nilutamide
• At least 4 weeks since prior hormonal therapy known to decrease PSA levels (including ketoconazole, aminoglutethimide, finasteride, or any systemic corticosteroid)
• Concurrent primary testicular androgen suppression therapy (e.g., with a LHRH analog) allowed
• No other concurrent hormonal therapy except:
• Steroids for adrenal insufficiency
• Hormones for non-disease-related conditions (e.g., insulin for diabetes)
• Intermittent dexamethasone as an antiemetic

Radiotherapy

• At least 4 weeks since prior radiotherapy and recovered
• At least 8 weeks since prior strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium
• No concurrent palliative radiotherapy

Surgery

• See Disease Characteristics
• At least 4 weeks since prior major surgery and recovered

Other

• At least 4 weeks since prior herbal product known to decrease PSA levels (including saw palmetto, PC-SPES)
• More than 1 week since prior sulindac
• No concurrent sulindac
• No concurrent chronic nonsteroidal anti-inflammatory drugs (including COX-2 inhibitors and salicylates such as aspirin, mesalamine, salsalate, and sulfasalazine)
• Concurrent ibuprofen and naproxen allowed
• Low-dose aspirin (e.g., 81 mg/day) for cardiovascular prevention allowed
• No concurrent full-dose oral or parenteral anticoagulation therapy
• Concurrent bisphosphonate therapy allowed provided therapy was initiated at least 4 weeks before study and disease has progressed despite therapy

Alabama
      Northeast Alabama Regional Medical Center, Anniston,  Alabama,  36207,  United States
California
      Cedars-Sinai Comprehensive Cancer Center at Cedars-Sinai Medical Center, Los Angeles,  California,  90048,  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 Medical Center - San Diego, San Diego,  California,  92161,  United States
      Veterans Affairs Medical Center - San Francisco, San Francisco,  California,  94121,  United States
Delaware
      CCOP - Christiana Care Health Services, Newark,  Delaware,  19713,  United States
District of Columbia
      Lombardi Cancer Center of Georgetown University Medical Center, Washington,  District of Columbia,  20007,  United States
      Veterans Affairs Medical Center - Washington, DC, Washington,  District of Columbia,  20422,  United States
      Walter Reed Army Medical Center, Washington,  District of Columbia,  20307-5000,  United States
Florida
      Broward General Medical Center, Fort Lauderdale,  Florida,  33316,  United States
      CCOP - Mount Sinai Medical Center, Miami Beach,  Florida,  33140,  United States
      Florida Hospital Cancer Institute, Orlando,  Florida,  32804,  United States
      Memorial Regional Hospital Comprehensive Cancer Center, Hollywood,  Florida,  33021,  United States
      Palm Beach Cancer Institute, West Palm Beach,  Florida,  33401,  United States
Illinois
      Louis A. Weiss Memorial Hospital, Chicago,  Illinois,  60640,  United States
      MBCCOP - University of Illinois at Chicago, Chicago,  Illinois,  60612-7323,  United States
      Saint Anthony Medical Center, Rockford,  Illinois,  61108,  United States
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States
      Veterans Affairs Medical Center - Chicago (Westside Hospital), Chicago,  Illinois,  60612,  United States
      West Suburban Center for Cancer Care, River Forest,  Illinois,  60305,  United States
Indiana
      CCOP - Northern Indiana CR Consortium, South Bend,  Indiana,  46601,  United States
      Fort Wayne Medical Oncology and Hematology, Incorporated, Fort Wayne,  Indiana,  46885-5099,  United States
Iowa
      Holden Comprehensive Cancer Center at University of Iowa, Iowa City,  Iowa,  52242-1009,  United States
Kentucky
      Baptist Hospital East - Louisville, Louisville,  Kentucky,  40207,  United States
Maryland
      Marlene and Stewart Greenebaum Cancer Center, University of Maryland, Baltimore,  Maryland,  21201,  United States
      Veterans Affairs Medical Center - Baltimore, Baltimore,  Maryland,  21201,  United States
Massachusetts
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States
      University of Massachusetts Memorial Medical Center - University Campus, Worcester,  Massachusetts,  01655,  United States
Michigan
      Lakeland Medical Center - St. Joseph, Saint Joseph,  Michigan,  49085,  United States
Minnesota
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States
      Veterans Affairs Medical Center - Minneapolis, Minneapolis,  Minnesota,  55417,  United States
Missouri
      Barnes-Jewish Hospital, Saint Louis,  Missouri,  63110,  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
      Veterans Affairs Medical Center - Columbia (Truman Memorial), Columbia,  Missouri,  65201,  United States
Nebraska
      University of Nebraska Medical Center, Omaha,  Nebraska,  68198-7680,  United States
Nevada
      CCOP - Southern Nevada Cancer Research Foundation, Las Vegas,  Nevada,  89106,  United States
      Veterans Affairs Medical Center - Las Vegas, Las Vegas,  Nevada,  89106,  United States
New Hampshire
      Norris Cotton Cancer Center at Dartmouth Medical School, Lebanon,  New Hampshire,  03756-0002,  United States
New Jersey
      Cooper University Hospital, Camden,  New Jersey,  08103,  United States
New York
      CCOP - North Shore University Hospital, Manhasset,  New York,  11030,  United States
      CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C., Syracuse,  New York,  13217,  United States
      Elmhurst Hospital Center, Elmhurst,  New York,  11373,  United States
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States
      Mount Sinai Medical Center, NY, New York,  New York,  10029,  United States
      New York Weill Cornell Cancer Center at Cornell University, New York,  New York,  10021,  United States
      North Shore University Hospital, Manhasset,  New York,  11030,  United States
      Queens Cancer Center of Queens Hospital, Jamaica,  New York,  11432,  United States
      State University of New York - Upstate Medical University, Syracuse,  New York,  13210,  United States
      Veterans Affairs Medical Center - Buffalo, Buffalo,  New York,  14215,  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, Winston Salem,  North Carolina,  27104-4241,  United States
      Comprehensive Cancer Center at Wake Forest University, Winston Salem,  North Carolina,  27157-1082,  United States
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States
      FirstHealth Moore Regional Hospital, Pinehurst,  North Carolina,  28374,  United States
      Lenoir Memorial Hospital Cancer Center, Kinston,  North Carolina,  28503-1678,  United States
      Lineberger Comprehensive Cancer Center, UNC, Chapel Hill,  North Carolina,  27599-7295,  United States
      New Hanover Regional Medical Center, Wilmington,  North Carolina,  28402-9025,  United States
      NorthEast Oncology Associates, Concord,  North Carolina,  28025,  United States
      Veterans Affairs Medical Center - Asheville, Asheville,  North Carolina,  28805,  United States
      Veterans Affairs Medical Center - Durham, Durham,  North Carolina,  27705,  United States
North Dakota
      Veterans Affairs Medical Center - Fargo, Fargo,  North Dakota,  58102,  United States
Ohio
      Arthur G. James Cancer Hospital - Ohio State University, Columbus,  Ohio,  43210-1240,  United States
Pennsylvania
      Western Pennsylvania Hospital, Pittsburgh,  Pennsylvania,  15224,  United States
Rhode Island
      Lifespan: The Miriam Hospital, Providence,  Rhode Island,  02906,  United States
Texas
      Simmons Cancer Center at University of Texas Southwestern Medical Center - Dalas, Dallas,  Texas,  75235-9154,  United States
      Veterans Affairs Medical Center - Dallas, Dallas,  Texas,  75216,  United States
Vermont
      Green Mountain Oncology Group, Bennington,  Vermont,  05201,  United States
      Vermont Cancer Center at University of Vermont, Burlington,  Vermont,  05401-3498,  United States
      Veterans Affairs Medical Center - White River Junction, White River Junction,  Vermont,  05009,  United States
Virginia
      Martha Jefferson Hospital, Charlottesville,  Virginia,  22902,  United States
      MBCCOP - Massey Cancer Center, Richmond,  Virginia,  23298-0037,  United States
      Oncology and Hematology Associates of Southwest Virginia, Inc., Roanoke,  Virginia,  24014,  United States
      Virginia Oncology Associates - Norfolk, Norfolk,  Virginia,  23502,  United States
West Virginia
      St. Mary's Medical Center, Huntington,  West Virginia,  25701,  United States
Wisconsin
      Ministry Medical Group - Northern Region, Rhinelander,  Wisconsin,  54501,  United States
Canada, Quebec
      McGill University, Montreal,  Quebec,  H2W 1S6,  Canada
Puerto Rico
      University of Puerto Rico School of Medicine Medical Sciences Campus, San Juan,  00936-5067,  Puerto Rico

Study chairs or principal investigators

Nancy Ann Dawson, MD,  Study Chair,  University of Maryland Greenebaum Cancer Center   

Study ID Numbers:  CDR0000258766; CALGB-90004
Record last reviewed:  February 2004
Last Updated:  October 13, 2004
Record first received:  January 24, 2003
ClinicalTrials.gov Identifier:  NCT00052845
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08