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”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Active Control

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.

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

Lead Sponsor: Eastern Cooperative Oncology Group

Comprehensive Cancer Institute

Huntsville Alabama 35801 United States

CCOP - Mayo Clinic Scottsdale Oncology Program

Scottsdale Arizona 85259-5404 United States

Veterans Affairs Medical Center - Tucson

Tucson Arizona 85723 United States

Veterans Affairs Medical Center - Little Rock

Little Rock Arkansas 72205 United States

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

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

Walter Reed Army Medical Center

Washington District of Columbia 20307-5001 United States

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

Veterans Affairs Medical Center - Atlanta (Decatur)

Decatur Georgia 30033 United States

MBCCOP - Hawaii

Honolulu Hawaii 96813 United States

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 University Cancer Center

Indianapolis Indiana 46202-5289 United States

Veterans Affairs Medical Center - Indianapolis (Roudebush)

Indianapolis Indiana 46202 United States

CCOP - Cedar Rapids Oncology Project

Cedar Rapids Iowa 52403-1206 United States

Veterans Affairs Medical Center - Wichita

Wichita Kansas 67218 United States

Veterans Affairs Medical Center - Lexington

Lexington Kentucky 40502-2236 United States

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

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

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

Mayo Clinic Cancer Center

Rochester Minnesota 55905 United States

Veterans Affairs Medical Center - Jackson

Jackson Mississippi 39216 United States

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

CCOP - Southern Nevada Cancer Research Foundation

Las Vegas Nevada 89106 United States

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

Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School

New Brunswick New Jersey 08903 United States

MBCCOP - University of New Mexico HSC

Albuquerque New Mexico 87131 United States

Veterans Affairs Medical Center - Albuquerque

Albuquerque New Mexico 87108-5138 United States

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

Cape Fear Valley Health System

Fayetteville North Carolina 28302-2000 United States

CCOP - Southeast Cancer Control Consortium

Goldsboro North Carolina 27534-9479 United States

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 University Medical Center

Oklahoma City Oklahoma 73104 United States

Veterans Affairs Medical Center - Portland

Portland Oregon 97207 United States

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

Veterans Affairs Medical Center - Charleston

Charleston South Carolina 29401-5799 United States

CCOP - Sioux Community Cancer Consortium

Sioux Falls South Dakota 57104 United States

Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center

Nashville Tennessee 37232-6307 United States

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

Veterans Affairs Medical Center - Salt Lake City

Salt Lake City Utah 84148 United States

Martha Jefferson Hospital

Charlottesville Virginia 22902 United States

Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke

Roanoke Virginia 24014 United States

Veterans Affairs Medical Center - Seattle

Seattle Washington 98108 United States

St. Mary's Medical Center

Huntington West Virginia 25701 United States

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

Overall Clinical Trial Officials and Contacts

Michael A. Carducci, MD Study Chair Sidney Kimmel Comprehensive Cancer Center  

Information obtained from ClinicalTrials.gov on July 23, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00027859

Study ID Number: CDR0000069088

ClinicalTrials.gov Identifier: NCT00027859

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database