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

Prostate Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00027859
• Other study ID #: CDR0000069088
• Secondary ID: E1899SWOG-E1899C
• Status: Completed
• Phase: Phase 3
• Start date: October 8, 2003

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. primary completion date: December 2004
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• docetaxel

• estramustine phosphate sodium

• ketoconazole

• therapeutic hydrocortisone

Locations

Country	Name	City	State
United States	MBCCOP - University of New Mexico HSC	Albuquerque	New Mexico
United States	Veterans Affairs Medical Center - Albuquerque	Albuquerque	New Mexico
United States	Harrington Cancer Center	Amarillo	Texas
United States	Veterans Affairs Medical Center - Amarillo	Amarillo	Texas
United States	Medical Center of Aurora - South Campus	Aurora	Colorado
United States	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Boulder Community Hospital	Boulder	Colorado
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	CCOP - Cedar Rapids Oncology Project	Cedar Rapids	Iowa
United States	Veterans Affairs Medical Center - Charleston	Charleston	South Carolina
United States	Martha Jefferson Hospital	Charlottesville	Virginia
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Veterans Affairs Medical Center - Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado
United States	Ellis Fischel Cancer Center at University of Missouri - Columbia	Columbia	Missouri
United States	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University	Columbus	Ohio
United States	CCOP - Columbus	Columbus	Ohio
United States	CCOP - Geisinger Clinic and Medical Center	Danville	Pennsylvania
United States	Veterans Affairs Medical Center - Dayton	Dayton	Ohio
United States	CCOP - Central Illinois	Decatur	Illinois
United States	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois
United States	Veterans Affairs Medical Center - Atlanta (Decatur)	Decatur	Georgia
United States	CCOP - Colorado Cancer Research Program, Incorporated	Denver	Colorado
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - St. Luke's Medical Center	Denver	Colorado
United States	Rocky Mountain Cancer Centers - Denver Rose	Denver	Colorado
United States	St. Joseph Hospital	Denver	Colorado
United States	Veterans Affairs Medical Center - Denver	Denver	Colorado
United States	Veterans Affairs Medical Center - Detroit	Detroit	Michigan
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Swedish Medical Center	Englewood	Colorado
United States	Cape Fear Valley Health System	Fayetteville	North Carolina
United States	CCOP - Southeast Cancer Control Consortium	Goldsboro	North Carolina
United States	CCOP - St. Vincent Hospital Cancer Center, Green Bay	Green Bay	Wisconsin
United States	Veterans Affairs Medical Center - Hines	Hines	Illinois
United States	Memorial Regional Cancer Center at Memorial Regional Hospital	Hollywood	Florida
United States	MBCCOP - Hawaii	Honolulu	Hawaii
United States	New Hampshire Oncology-Hematology, PA - Hooksett	Hooksett	New Hampshire
United States	St. Mary's Medical Center	Huntington	West Virginia
United States	Comprehensive Cancer Institute	Huntsville	Alabama
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	Veterans Affairs Medical Center - Indianapolis (Roudebush)	Indianapolis	Indiana
United States	Veterans Affairs Medical Center - Jackson	Jackson	Mississippi
United States	CCOP - Kalamazoo	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	CCOP - Kansas City	Kansas City	Missouri
United States	Rebecca and John Moores UCSD Cancer Center	La Jolla	California
United States	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Veterans Affairs Medical Center - Lexington	Lexington	Kentucky
United States	Veterans Affairs Medical Center - Little Rock	Little Rock	Arkansas
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Hope Cancer Care Center at Longmont United Hospital	Longmont	Colorado
United States	Cedars-Sinai Comprehensive Cancer Center at Cedars-Sinai Medical Center	Los Angeles	California
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	Veterans Affairs Outpatient Clinic - Martinez	Martinez	California
United States	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin
United States	Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center	Nashville	Tennessee
United States	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	CCOP - Ochsner	New Orleans	Louisiana
United States	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana
United States	Veterans Affairs Medical Center - New Orleans	New Orleans	Louisiana
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Mount Sinai Medical Center	New York	New York
United States	NYU School of Medicine's Kaplan Comprehensive Cancer Center	New York	New York
United States	Oklahoma University Medical Center	Oklahoma City	Oklahoma
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Abramson Cancer Center at the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Western Pennsylvania Hospital	Pittsburgh	Pennsylvania
United States	Veterans Affairs Medical Center - Portland	Portland	Oregon
United States	St. Mary-Corwin Regional Medical Center	Pueblo	Colorado
United States	West Suburban Center for Cancer Care	River Forest	Illinois
United States	Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke	Roanoke	Virginia
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph	Saint Joseph	Michigan
United States	Missouri Baptist Cancer Center	Saint Louis	Missouri
United States	Veterans Affairs Medical Center - Salt Lake City	Salt Lake City	Utah
United States	Veterans Affairs Medical Center - San Antonio (Murphy)	San Antonio	Texas
United States	Naval Medical Center - San Diego	San Diego	California
United States	UCSF Comprehensive Cancer Center	San Francisco	California
United States	CCOP - Mayo Clinic Scottsdale Oncology Program	Scottsdale	Arizona
United States	Veterans Affairs Medical Center - Seattle	Seattle	Washington
United States	Veterans Affairs Medical Center - Shreveport	Shreveport	Louisiana
United States	CCOP - Sioux Community Cancer Consortium	Sioux Falls	South Dakota
United States	Veterans Affairs Medical Center - Syracuse	Syracuse	New York
United States	H. Lee Moffitt Cancer Center and Research Institute at University of South Florida	Tampa	Florida
United States	Veterans Affairs Medical Center - Tampa (Haley)	Tampa	Florida
United States	CCOP - Scott and White Hospital	Temple	Texas
United States	Veterans Affairs Medical Center - Temple	Temple	Texas
United States	Rocky Mountain Cancer Centers - Thornton	Thornton	Colorado
United States	CCOP - Toledo Community Hospital	Toledo	Ohio
United States	Veterans Affairs Medical Center - Tucson	Tucson	Arizona
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	Walter Reed Army Medical Center	Washington	District of Columbia
United States	Veterans Affairs Medical Center - Wichita	Wichita	Kansas

Sponsors (4)

Lead Sponsor	Collaborator
Eastern Cooperative Oncology Group	Cancer and Leukemia Group B, National Cancer Institute (NCI), SWOG Cancer Research Network

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation