Clinical trial NCT00027859: Hormone Therapy Compared With Combination Chemotherapy in Treating Patients With Prostate Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostate Cancer
Keywords: adenocarcinoma of the prostate
stage III prostate cancer
Lead sponsor: Eastern Cooperative Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: SWOG Cancer Research Network
name: Cancer and Leukemia Group B
First posted: 2003-01-27
Sex: MALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Comprehensive Cancer Institute
state: Alabama
city: Scottsdale
country: United States
facility: CCOP - Mayo Clinic Scottsdale Oncology Program
state: Arizona
city: Tucson
country: United States
facility: Veterans Affairs Medical Center - Tucson
state: Arizona
city: Little Rock
country: United States
facility: Veterans Affairs Medical Center - Little Rock
state: Arkansas
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: La Jolla
country: United States
facility: Rebecca and John Moores UCSD Cancer Center
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Comprehensive Cancer Center at Cedars-Sinai Medical Center
state: California
city: Martinez
country: United States
facility: Veterans Affairs Outpatient Clinic - Martinez
state: California
city: San Diego
country: United States
facility: Naval Medical Center - San Diego
state: California
city: San Francisco
country: United States
facility: UCSF Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: Medical Center of Aurora - South Campus
state: Colorado
city: Boulder
country: United States
facility: Boulder Community Hospital
state: Colorado
city: Colorado Springs
country: United States
facility: Penrose Cancer Center at Penrose Hospital
state: Colorado
city: Denver
country: United States
facility: Porter Adventist Hospital
state: Colorado
city: Denver
country: United States
facility: St. Joseph Hospital
state: Colorado
city: Denver
country: United States
facility: Presbyterian - St. Luke's Medical Center
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers - Denver Rose
state: Colorado
city: Denver
country: United States
facility: Veterans Affairs Medical Center - Denver
state: Colorado
city: Denver
country: United States
facility: CCOP - Colorado Cancer Research Program, Incorporated
state: Colorado
city: Englewood
country: United States
facility: Swedish Medical Center
state: Colorado
city: Lone Tree
country: United States
facility: Sky Ridge Medical Center
state: Colorado
city: Longmont
country: United States
facility: Hope Cancer Care Center at Longmont United Hospital
state: Colorado
city: Pueblo
country: United States
facility: St. Mary-Corwin Regional Medical Center
state: Colorado
city: Thornton
country: United States
facility: Rocky Mountain Cancer Centers - Thornton
state: Colorado
city: Washington
country: United States
facility: Walter Reed Army Medical Center
state: District of Columbia
city: Hollywood
country: United States
facility: Memorial Regional Cancer Center at Memorial Regional Hospital
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
state: Florida
city: Tampa
country: United States
facility: Veterans Affairs Medical Center - Tampa (Haley)
state: Florida
city: Decatur
country: United States
facility: Veterans Affairs Medical Center - Atlanta (Decatur)
state: Georgia
city: Honolulu
country: United States
facility: MBCCOP - Hawaii
state: Hawaii
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Decatur
country: United States
facility: CCOP - Central Illinois
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital Cancer Care Institute
state: Illinois
city: Hines
country: United States
facility: Veterans Affairs Medical Center - Hines
state: Illinois
city: Peoria
country: United States
facility: CCOP - Illinois Oncology Research Association
state: Illinois
city: River Forest
country: United States
facility: West Suburban Center for Cancer Care
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: Veterans Affairs Medical Center - Indianapolis (Roudebush)
state: Indiana
city: Cedar Rapids
country: United States
facility: CCOP - Cedar Rapids Oncology Project
state: Iowa
city: Wichita
country: United States
facility: Veterans Affairs Medical Center - Wichita
state: Kansas
city: Lexington
country: United States
facility: Veterans Affairs Medical Center - Lexington
state: Kentucky
city: New Orleans
country: United States
facility: MBCCOP - LSU Health Sciences Center
state: Louisiana
city: New Orleans
country: United States
facility: Veterans Affairs Medical Center - New Orleans
state: Louisiana
city: New Orleans
country: United States
facility: CCOP - Ochsner
state: Louisiana
city: Shreveport
country: United States
facility: Veterans Affairs Medical Center - Shreveport
state: Louisiana
city: Baltimore
country: United States
facility: Greenebaum Cancer Center at University of Maryland Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Detroit
country: United States
facility: Veterans Affairs Medical Center - Detroit
state: Michigan
city: Kalamazoo
country: United States
facility: CCOP - Kalamazoo
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Saint Joseph
country: United States
facility: Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Jackson
country: United States
facility: Veterans Affairs Medical Center - Jackson
state: Mississippi
city: Columbia
country: United States
facility: Ellis Fischel Cancer Center at University of Missouri - Columbia
state: Missouri
city: Kansas City
country: United States
facility: CCOP - Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: Missouri Baptist Cancer Center
state: Missouri
city: Las Vegas
country: United States
facility: CCOP - Southern Nevada Cancer Research Foundation
state: Nevada
city: Hooksett
country: United States
facility: New Hampshire Oncology-Hematology, PA - Hooksett
state: New Hampshire
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
state: New Jersey
city: Albuquerque
country: United States
facility: Veterans Affairs Medical Center - Albuquerque
state: New Mexico
city: Albuquerque
country: United States
facility: MBCCOP - University of New Mexico HSC
state: New Mexico
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: NYU School of Medicine's Kaplan Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Syracuse
country: United States
facility: Veterans Affairs Medical Center - Syracuse
state: New York
city: Fayetteville
country: United States
facility: Cape Fear Valley Health System
state: North Carolina
city: Goldsboro
country: United States
facility: CCOP - Southeast Cancer Control Consortium
state: North Carolina
city: Cincinnati
country: United States
facility: Veterans Affairs Medical Center - Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Columbus
country: United States
facility: CCOP - Columbus
state: Ohio
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University
state: Ohio
city: Dayton
country: United States
facility: Veterans Affairs Medical Center - Dayton
state: Ohio
city: Toledo
country: United States
facility: CCOP - Toledo Community Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Medical Center
state: Oklahoma
city: Portland
country: United States
facility: Veterans Affairs Medical Center - Portland
state: Oregon
city: Danville
country: United States
facility: CCOP - Geisinger Clinic and Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Abramson Cancer Center at the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Western Pennsylvania Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Veterans Affairs Medical Center - Charleston
state: South Carolina
city: Sioux Falls
country: United States
facility: CCOP - Sioux Community Cancer Consortium
state: South Dakota
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center
state: Tennessee
city: Amarillo
country: United States
facility: Harrington Cancer Center
state: Texas
city: Amarillo
country: United States
facility: Veterans Affairs Medical Center - Amarillo
state: Texas
city: San Antonio
country: United States
facility: Veterans Affairs Medical Center - San Antonio (Murphy)
state: Texas
city: Temple
country: United States
facility: Veterans Affairs Medical Center - Temple
state: Texas
city: Temple
country: United States
facility: CCOP - Scott and White Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Veterans Affairs Medical Center - Salt Lake City
state: Utah
city: Charlottesville
country: United States
facility: Martha Jefferson Hospital
state: Virginia
city: Roanoke
country: United States
facility: Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke
state: Virginia
city: Seattle
country: United States
facility: Veterans Affairs Medical Center - Seattle
state: Washington
city: Huntington
country: United States
facility: St. Mary's Medical Center
state: West Virginia
city: Green Bay
country: United States
facility: CCOP - St. Vincent Hospital Cancer Center, Green Bay
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Cancer Center
state: Wisconsin
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Michael A. Carducci, MD
role: STUDY_CHAIR
affiliation: Veterans Affairs Medical Center - Hines
name: Nirmala Bhoopalam, MD
role: STUDY_CHAIR
affiliation: Deaconess Medical Center, Spokane, Washington
name: Gregory P. Swanson, MD
role: STUDY_CHAIR
affiliation: National Cancer Institute (NCI)
name: William Dahut, MD
role: STUDY_CHAIR
References:
citation: Walczak JR, Carducci MA; Eastern Cooperative Oncology Group E1899. Phase 3 randomized trial evaluating second-line hormonal therapy versus docetaxel-estramustine combination chemotherapy on progression-free survival in asymptomatic patients with a rising prostate-specific antigen level after hormonal therapy for prostate cancer: an Eastern Cooperative Oncology Group (E1899), Intergroup/Clinical Trials Support Unit study. Urology. 2003 Dec 29;62 Suppl 1:141-6. doi: 10.1016/j.urology.2003.09.006.