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

Condition(s) targeted: Prostate Cancer

Intervention: docetaxel (Drug); estramustine phosphate sodium (Drug); ketoconazole (Drug); therapeutic hydrocortisone (Drug)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: Eastern Cooperative Oncology Group

Official(s) and/or principal investigator(s):
Michael A. Carducci, MD, Study Chair, Affiliation: Sidney Kimmel Comprehensive Cancer Center
Nirmala Bhoopalam, MD, Study Chair, Affiliation: Veterans Affairs Medical Center - Hines
Gregory P. Swanson, MD, Affiliation: Deaconess Medical Center, Spokane, Washington
William Dahut, MD, Study Chair, Affiliation: National Cancer Institute (NCI)

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.

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 design: Treatment, Randomized, Active Control

Detailed description: 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Male.

Criteria:

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

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

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

Starting date: May 2003
Last updated: May 23, 2008