Hormone Therapy Compared With Combination Chemotherapy in Treating Patients With Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00027859
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : January 27, 2010
National Cancer Institute (NCI)
Southwest Oncology Group
Cancer and Leukemia Group B
Information provided by:
Eastern Cooperative Oncology Group

Brief Summary:

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 or disease Intervention/treatment Phase
Prostate Cancer Drug: docetaxel Drug: estramustine phosphate sodium Drug: ketoconazole Drug: therapeutic hydrocortisone Phase 3

Detailed Description:


  • 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.

Study Type : Interventional  (Clinical Trial)
Allocation: Randomized
Primary Purpose: Treatment
Official Title: A Phase III Randomized Trial for Evaluating Second Line Hormonal Therapy (Ketoconazole/Hydrocortisone) Versus Paclitaxel/Estramustine Combination Chemotherapy on Progression Free Survival in Asymptomatic Patients With a Rising PSA After Hormonal Therapy for Prostate Cancer
Study Start Date : May 2003
Actual Primary Completion Date : December 2004

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
U.S. FDA Resources

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No


  • 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)



  • 18 and over

Performance status:

  • ECOG 0-1

Life expectancy:

  • Not specified


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


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


  • Creatinine no greater than 1.7 mg/dL


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


  • 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


Biologic therapy:

  • Not specified


  • At least 5 years since prior systemic chemotherapy

Endocrine therapy:

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


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


  • See Disease Characteristics


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00027859

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

Publications of Results:
Responsible Party: Group Chair, Eastern Cooperative Oncology Group Identifier: NCT00027859     History of Changes
Other Study ID Numbers: CDR0000069088
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: January 27, 2010
Last Verified: January 2010

Keywords provided by Eastern Cooperative Oncology Group:
adenocarcinoma of the prostate
stage III prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Cortisol succinate
Anti-Inflammatory Agents
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors
Antineoplastic Agents, Alkylating
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Hormonal