RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as bevacizumab may stop the growth of cancer cells by stopping blood flow to the tumor. Combining monoclonal antibody therapy with chemotherapy may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy plus monoclonal antibody therapy in treating patients who have metastatic prostate cancer that has not responded to previous hormone therapy.

Condition	Treatment or Intervention	Phase
stage IV prostate cancer adenocarcinoma of the prostate recurrent prostate cancer	Procedure: chemotherapy  Procedure: biological response modifier therapy  Procedure: monoclonal antibody therapy  Procedure: growth factor antagonist therapy  Procedure: antibody therapy  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Drug: bevacizumab  Drug: docetaxel  Drug: estramustine	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the time to objective progression, response rate, and duration of response in patients with hormone-refractory metastatic prostate cancer treated with bevacizumab, estramustine, and docetaxel. II. Determine the toxicity of this regimen in these patients. III. Assess the relationship of baseline vascular endothelial growth factor levels in urine and plasma and changes in these levels with response and duration of response in patients treated with this regimen.

PROTOCOL OUTLINE: This is a multicenter study. Patients are stratified according to urine vascular endothelial growth factor level (low vs high). Patients receive oral estramustine 3 times daily on days 1-5 and docetaxel IV over 1 hour followed by bevacizumab IV over 30-90 minutes on day 2. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed at least every 3 months for 2 years.

PROJECTED ACCRUAL: A total of 72 patients (36 per stratum) will be accrued for this study within 18 months.

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Histologically confirmed adenocarcinoma of the prostate

Metastatic disease after at least 1 prior endocrine manipulation with orchiectomy, LHRH agonist, or diethylstilbestrol

• Refractory to standard hormonal therapy

Measurable disease with any PSA level

• Target lesion at least 20 mm by physical exam or chest x-ray OR
• At least 10 mm by spiral CT scan
• Histological confirmation of neoplastic nature required if disease is confined to only 1 target lesion

OR

Non-measurable disease with PSA at least 5 ng/mL

• Bone lesions
• Pleural or pericardial effusions or ascites
• CNS lesions or leptomeningeal disease
• Previously irradiated lesions, unless progression documented after radiotherapy

Progressive disease

• Objective evidence of greater than 20% increase in the sum of the longest diameters of target lesions for measurable disease
• Progression by bone scan or PSA for non-measurable disease

Castrate levels of testosterone must be maintained

Serum testosterone no greater than 50 ng/mL for patients without prior bilateral orchiectomy

--Prior/Concurrent Therapy--

Biologic therapy: No prior antiangiogenesis agents, including thalidomide and bevacizumab

Chemotherapy:

• No prior cytotoxic chemotherapy, including estramustine and suramin
• No other concurrent chemotherapy

Endocrine therapy:

• See Disease Characteristics
• At least 4 weeks since prior antiandrogen therapy except testicular androgen suppression (e.g., LHRH analog)
• No concurrent hormonal therapy except steroids for adrenal insufficiency or nondisease-related conditions (e.g., insulin for diabetes)
• Concurrent testicular androgen suppression required, if initiated before study

Radiotherapy:

• See Disease Characteristics
• 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 radiotherapy

Surgery:

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

Other:

• No requirement for full-dose or parenteral anticoagulation
• Daily prophylactic aspirin allowed

--Patient Characteristics--

Age: Any age

Performance status: CTC (ECOG) 0-2

Life expectancy: Not specified

Hematopoietic:

• Granulocyte count at least 1,500/mm3
• Platelet count at least 100,000/mm3

Hepatic:

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

Renal:

• Creatinine no greater than 1.5 times ULN
• Urinalysis no greater than 1+ protein on dipstick

Cardiovascular:

• No myocardial infarction or significant change in anginal pattern within the past year
• No congestive heart failure (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
• Fertile patients must use effective contraception

Alabama
      Veterans Affairs Medical Center - Birmingham, Birmingham,  Alabama,  35233-1996,  United States
California
      Cedars-Sinai Medical Center, Los Angeles,  California,  90048,  United States
      UCSF Cancer Center and Cancer Research Institute, San Francisco,  California,  94143-0128,  United States
      University of California San Diego Cancer Center, La Jolla,  California,  92093-0658,  United States
      Veterans Affairs Medical Center - San Francisco, San Francisco,  California,  94121,  United States
Delaware
      CCOP - Christiana Care Health Services, Wilmington,  Delaware,  19899,  United States
District of Columbia
      Lombardi Cancer Center, Washington,  District of Columbia,  20007,  United States
      Walter Reed Army Medical Center, Washington,  District of Columbia,  20307-5000,  United States
Florida
      CCOP - Mount Sinai Medical Center, Miami Beach,  Florida,  33140,  United States
Illinois
      MBCCOP - University of Illinois at Chicago, Chicago,  Illinois,  60612-7323,  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
Indiana
      CCOP - Northern Indiana CR Consortium, South Bend,  Indiana,  46601,  United States
Iowa
      Holden Comprehensive Cancer Center, Iowa City,  Iowa,  52242-1009,  United States
Maine
      Veterans Affairs Medical Center - Togus, Togus,  Maine,  04330,  United States
Maryland
      Marlene & Stewart Greenebaum Cancer Center, University of Maryland, Baltimore,  Maryland,  21201,  United States
Massachusetts
      Dana-Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States
      University of Massachusetts Memorial Medical Center, Worcester,  Massachusetts,  01655,  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 - 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
      Washington University Siteman Cancer Center, Saint Louis,  Missouri,  63110,  United States
Nebraska
      University of Nebraska Medical Center, Omaha,  Nebraska,  68198-3330,  United States
Nevada
      CCOP - Southern Nevada Cancer Research Foundation, Las Vegas,  Nevada,  89106,  United States
New Hampshire
      Norris Cotton Cancer Center, Lebanon,  New Hampshire,  03756-0002,  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
      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 Presbyterian Hospital - Cornell Campus, New York,  New York,  10021,  United States
      Roswell Park Cancer Institute, Buffalo,  New York,  14263-0001,  United States
      Schneider Children's Hospital at North Shore, Manhasset,  New York,  11030,  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
      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
      Lineberger Comprehensive Cancer Center, UNC, Chapel Hill,  North Carolina,  27599-7295,  United States
      Veterans Affairs Medical Center - Durham, Durham,  North Carolina,  27705,  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
      Rhode Island Hospital, Providence,  Rhode Island,  02903,  United States
Tennessee
      University of Tennessee, Memphis Cancer Center, Memphis,  Tennessee,  38103,  United States
      Veterans Affairs Medical Center - Memphis, Memphis,  Tennessee,  38104,  United States
Texas
      Simmons Cancer Center - Dallas, Dallas,  Texas,  75235-9154,  United States
Vermont
      Green Mountain Oncology Group, Bennington,  Vermont,  05201,  United States
      Vermont Cancer Center, Burlington,  Vermont,  05401-3498,  United States
      Veterans Affairs Medical Center - White River Junction, White River Junction,  Vermont,  05009,  United States
Virginia
      MBCCOP - Massey Cancer Center, Richmond,  Virginia,  23298-0037,  United States
      Veterans Affairs Medical Center - Richmond, Richmond,  Virginia,  23249,  United States
Canada, Quebec
      McGill University, Montreal,  Quebec,  H2W 1S6,  Canada

Study chairs or principal investigators

Joel Picus,  Study Chair,  Cancer and Leukemia Group B   

Study ID Numbers:  CDR0000068595; CLB-90006
Record last reviewed:  June 2003
Last Updated:  October 13, 2004
Record first received:  May 6, 2001
ClinicalTrials.gov Identifier:  NCT00016107
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08