Hormone Therapy in Treating Patients With Rising PSA Levels Following Radiation Therapy for Prostate Cancer - Full Text View

Sponsor:	NCIC Clinical Trials Group
Collaborators:	National Cancer Institute (NCI) Southwest Oncology Group
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00003653

Purpose

RATIONALE: Androgens can stimulate the growth of prostate cancer cells. Hormone therapy may fight prostate cancer by reducing the production of androgens. It is not yet known which androgen suppression regimen is more effective for prostate cancer.

PURPOSE: This randomized phase III trial is studying two hormone therapy regimens and comparing them to see how well they work in treating patients with rising PSA levels following radiation therapy for prostate cancer.

Condition	Intervention	Phase
Prostate Cancer	Drug: bicalutamide Drug: buserelin Drug: cyproterone acetate Drug: flutamide Drug: goserelin Drug: leuprolide acetate Drug: nilutamide Procedure: orchiectomy	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
Official Title:	A Phase III Randomized Trial Comparing Intermittent Versus Continuous Androgen Suppression for Patients With Prostate-Specific-Antigen Progression in the Clinical Absence of Distant Metastases Following Radiotherapy for Prostate Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Prostate Cancer

Drug Information available for: Flutamide Leuprolide Buserelin Nilutamide Goserelin Buserelin acetate Leuprolide acetate Bicalutamide Cyproterone acetate Cyproterone

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Overall survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

Time to hormone resistance [ Designated as safety issue: No ]
Quality of life by European Organization for Research of the Treatment of Cancer Quality of Life Questionnaire-C30+ (EORTC QLQ-C30+) trial specific checklist [ Designated as safety issue: No ]
Serum cholesterol, high-density lipoprotein, and low-density lipoprotein levels [ Designated as safety issue: No ]
Duration of treatment and non-treatment interval during intermittent androgen suppression arm only [ Designated as safety issue: No ]
Time to testosterone recovery during intermittent androgen suppression arm only [ Designated as safety issue: No ]
Time to recovery of potency during intermittent androgen suppression arm only [ Designated as safety issue: No ]

Estimated Enrollment:	1386
Study Start Date:	January 1999

Detailed Description:

OBJECTIVES:

Compare the survival of prostate cancer patients with prostate-specific antigen progression in the clinical absence of distant metastases after prior radical radiotherapy treated with intermittent androgen suppression (IAS) vs continuous androgen deprivation (CAD).
Compare the time to the development of hormone resistance in patients treated with these regimens.
Compare the quality of life of patients treated with these regimens.
Compare the serum cholesterol and HDL/LDL levels at 3 years with those at baseline and compare them annually in patients treated with these regimens.
Evaluate the duration of treatment and non-treatment intervals, time to testosterone recovery (return to pre-therapy levels), and time to recover potency in patients treated with IAS.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior radical prostatectomy (yes vs no), time since completion of prior radical radiotherapy (1 to 3 years vs 3 years or more), baseline prostate-specific antigen (PSA) value (3-15 ng/mL vs greater than 15 ng/mL), and prior hormonal therapy (neo-adjuvant, concurrent, or adjuvant cytoreduction in association with the radical radiotherapy treatment or prostatectomy for a maximum duration of 12 months and completed at least 12 months prior to randomization) (yes vs no). Patients are randomized to one of two treatment arms.

Arm I: Patients undergo intermittent androgen suppression (IAS). Patients receive luteinizing hormone-releasing hormone (LHRH) analog (buserelin [BSRL], goserelin [ZDX], or leuprolide [LEUP]) and an antiandrogen (nilutamide [ANAN], flutamide [FLUT], bicalutamide [CDX], or cyproterone acetate [CPTR]) for 8 months. Patients receive LHRH analog by subcutaneous (SC) or intramuscular (IM) implant every 1-4 months beginning within 5 days of randomization and oral antiandrogen 1-3 times daily, depending on the actual LHRH analog and antiandrogen. PSA levels are monitored every 2 months. If PSA falls to normal during the 8-month treatment period, therapy stops until levels rise to 10 ng/mL, at which time IAS resumes for another 8-month period. IAS continues as long as PSA levels are controlled. At the time of disease progression, patients begin continuous hormonal treatment similar to arm II.
Arm II: Patients undergo continuous androgen deprivation without scheduled interruptions. Patients receive LHRH analog (BSRL, ZDX, or LEUP) with an antiandrogen (ANAN, FLUT, CDX, or CPTR) OR undergo bilateral orchiectomy within 5 days of randomization and receive an antiandrogen. Patients receive LHRH analog by SC or IM implant every 1-4 months beginning within 5 days of randomization and oral antiandrogen 1-3 times daily, depending on the actual LHRH analog and antiandrogen. PSA levels are monitored every 2 months. Treatment continues until hormone resistance develops.

Patients receiving LHRH analog may begin antiandrogen therapy either prior to or simultaneously with LHRH analog and must continue antiandrogen therapy for at least 4 weeks to block tumor flare.

Quality of life is assessed at randomization, every 4 months for 2 years, every 8 months until development of hormone resistance, at the time of hormone resistance, and then annually thereafter.

Patients are followed annually for survival.

PROJECTED ACCRUAL: A total of 1,386 patients will be accrued for this study within 7 years.

Eligibility

Ages Eligible for Study:	16 Years and older
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically proven adenocarcinoma of the prostate prior to the initiation of radiotherapy
Prior pelvic radiotherapy for prostate cancer, either post-radical prostatectomy or as primary management
- More than 30 months since prior brachytherapy with curative intent
Prostate-specific antigen must be rising and greater than 3 ng/mL and higher than the lowest level recorded previously since the end of radiotherapy (i.e., higher than the post-radiotherapy nadir)
Total testosterone greater than 5 nmol/L
No definite evidence of metastatic disease
- Chest x-ray and bone scan negative for metastases
- Radiological changes compatible with nonmalignant diseases allowed
Clinical evidence of local disease allowed

PATIENT CHARACTERISTICS:

Age:

16 and over (18 and over for participating centers in the United Kingdom)

Performance status:

ECOG 0-1

Life expectancy:

More than 5 years

Hematopoietic:

Not specified

Hepatic:

Bilirubin no greater than 1.5 times upper limit of normal (ULN)
AST/ALT no greater than 1.5 times ULN
LDH no greater than 1.5 times ULN
No chronic liver disease

Renal:

Creatinine no greater than 1.5 times ULN

Other:

Sufficiently fluent and willing to complete the quality of life questionnaire in either English or French
Fertile patients must use effective contraception
No other malignancy within the past 5 years except curatively treated basal or squamous cell skin cancer or superficial bladder cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

No prior or concurrent biologic therapy

Chemotherapy:

No prior or concurrent chemotherapy

Endocrine therapy:

Prior hormonal therapy administered prior to, during, or immediately after radical radiotherapy or prostatectomy allowed provided duration was no longer than 12 months
- At least 12 months since prior hormonal therapy

Radiotherapy:

See Disease Characteristics
At least 12 months since prior radiotherapy
No concurrent palliative radiotherapy

Surgery:

See Disease Characteristics
See Endocrine therapy

Other:

No concurrent bisphosphonates

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003653

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Locations

United States, Alaska
Fairbanks Cancer Treatment Center at Fairbanks Memorial Hospital
Fairbanks, Alaska, United States, 99701
United States, Arizona
Banner Good Samaritan Medical Center
Phoenix, Arizona, United States, 85006
Banner Thunderbird Medical Center
Phoenix, Arizona, United States, 85306
CCOP - Western Regional, Arizona
Phoenix, Arizona, United States, 85006
St. Joseph's Hospital and Medical Center
Phoenix, Arizona, United States, 85013
United States, Arkansas
Highlands Oncology Group - Springdale
Springdale, Arkansas, United States, 72764
United States, California
Cancer Center of Santa Barbara
Snata Barbara, California, United States, 93105
Memorial Medical Center Cancer Services
Modesto, California, United States, 95355
Sansum Medical Clinic
Santa Barbara, California, United States, 93105
Santa Barbara Hematology Oncology - Lompoc
Lompoc, California, United States, 93438
Santa Barbara Hematology Oncology - Solvang
Solvang, California, United States, 93463
Santa Barbara Hematology Oncology Medical Group at Cancer Center of Santa Barbara
Santa Barbara, California, United States, 93105
Torrance Memorial Medical Center
Torrance, California, United States, 90509
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States, 90033-0804
United States, Colorado
Veterans Affairs Medical Center - Denver
Denver, Colorado, United States, 80220
Exempla Lutheran Medical Center
Wheat Ridge, Colorado, United States, 80033
Montrose Memorial Hospital Cancer Center
Montrose, Colorado, United States, 81401
University of Colorado Cancer Center at University of Colorado Health Sciences Center
Denver, Colorado, United States, 80217-3364
Denver Health Medical Center
Denver, Colorado, United States, 80204
United States, Florida
Ella Milbank Foshay Cancer Center at Jupiter Medical Center
Jupiter, Florida, United States, 33458
United States, Hawaii
Tripler Army Medical Center
Honolulu, Hawaii, United States, 96859
United States, Idaho
North Idaho Cancer Center
Coeur D'Alene, Idaho, United States, 83814
United States, Illinois
Carle Cancer Center at Carle Foundation Hospital
Urbana, Illinois, United States, 61801
CCOP - Carle Cancer Center
Urbana, Illinois, United States, 61801
Decatur Memorial Hospital Cancer Care Institute
Decatur, Illinois, United States, 62526
Ingalls Cancer Care Center at Ingalls Memorial Hospital
Harvey, Illinois, United States, 60426
Joliet Oncology Hematology Associates, Limited - West
Joliet, Illinois, United States, 60435
Rush-Copley Cancer Care Center
Aurora, Illinois, United States, 60507
United States, Indiana
Saint Anthony Memorial Health Centers
Michigan City, Indiana, United States, 46360
United States, Iowa
CCOP - Iowa Oncology Research Association
Des Moines, Iowa, United States, 50309
Hematology Oncology Associates of the Quad Cities
Bettendorf, Iowa, United States, 52722
McFarland Clinic, P.C.
Ames, Iowa, United States, 50010
Wendt Regional Cancer Center at Finley Hospital
Dubuque, Iowa, United States, 52001
United States, Kansas
Cancer Center of Kansas - Dodge City
Dodge City, Kansas, United States, 67801
Veterans Affairs Medical Center - Wichita
Wichita, Kansas, United States, 67218
Via Christi Cancer Center at Via Christi Regional Medical Center
Wichita, Kansas, United States, 67214
United States, Louisiana
Feist-Weiller Cancer Center at Louisiana State University Health Sciences
Shreveport, Louisiana, United States, 71130
Louisiana State University Health Sciences Center - Monroe
Monroe, Louisiana, United States, 71210
Veterans Affairs Medical Center - Shreveport
Shreveport, Louisiana, United States, 71101
United States, Massachusetts
Cancer Research Center at Boston Medical Center
Boston, Massachusetts, United States, 02118
South Suburban Oncology Center
Quincy, Massachusetts, United States, 02169
United States, Michigan
Breslin Cancer Center at Ingham Regional Medical Center
East Lansing, Michigan, United States, 48824-1313
Foote Hospital
Jackson, Michigan, United States, 49201
St. Joseph Mercy Cancer Center at St. Joseph Mercy Hospital
Ann Arbor, Michigan, United States, 48106-0995
Josephine Ford Cancer Center at Henry Ford Hospital
Detroit, Michigan, United States, 48202
Seton Cancer Institute - Saginaw
Saginaw, Michigan, United States, 48601
St. John Macomb Hospital
Warren, Michigan, United States, 48903
Genesys Hurley Cancer Institute
Flint, Michigan, United States, 48532
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109
West Michigan Cancer Center
Kalamazoo, Michigan, United States, 49007
William Beaumont Hospital - Royal Oak Campus
Royal Oak, Michigan, United States, 48073
United States, Minnesota
Adult and Pediatric Urology, P.L.L.P.
St. Cloud, Minnesota, United States, 56303
Brainerd Medical Center
Brainerd, Minnesota, United States, 56401
CentraCare Clinic - River Campus
St. Cloud, Minnesota, United States, 56303
Chippewa County - Montevideo Hospital
Montevideo, Minnesota, United States, 56265
MeritCare Clinic - Bemidji
Bemidji, Minnesota, United States, 56601
United States, Missouri
Siteman Cancer Center at Barnes-Jewish Hospital
St Louis, Missouri, United States, 63110
United States, Montana
Great Falls Clinic
Great Falls, Montana, United States, 59405
Sletten Regional Cancer Institute
Great Falls, Montana, United States, 59405
United States, Nebraska
Good Samaritan Health Systems
Kearney, Nebraska, United States, 68847
United States, New Hampshire
Elliot Regional Cancer Center
Manchester, New Hampshire, United States, 03103
Lakes Region General Hospital
Laconia, New Hampshire, United States, 03246
New Hampshire Oncology-Hematology, PA - Hooksett
Hooksett, New Hampshire, United States, 03106
United States, New Jersey
Englewood Hospital and Medical Center
Englewood, New Jersey, United States, 07631
Valley Hospital - Ridgewood
Ridgewood, New Jersey, United States, 07450
Veterans Affairs Medical Center - East Orange
East Orange, New Jersey, United States, 07018-1095
United States, New York
Finger Lakes Hematology and Oncology
Clifton Springs, New York, United States, 14432
Highland Hospital of Rochester
Rochester, New York, United States, 14620
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, United States, 14642
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Veterans Affairs Medical Center - Brooklyn
Brooklyn, New York, United States, 11209
Veterans Affairs Medical Center - Syracuse
Syracuse, New York, United States, 13210
United States, North Carolina
CaroMont Cancer Center at Gaston Memorial Hospital
Gastonia, North Carolina, United States, 28053
Lenoir Memorial Cancer Center
Kinston, North Carolina, United States, 28501
Wayne Memorial Hospital, Incorporated
Goldsboro, North Carolina, United States, 27534
United States, North Dakota
CCOP - MeritCare Hospital
Fargo, North Dakota, United States, 58122
MeritCare Medical Group
Fargo, North Dakota, United States, 58122
United States, Ohio
Licking Memorial Cancer Care Program at Licking Memorial Hospital
Newark, Ohio, United States, 43055
Adena Regional Medical Center
Chillicothe, Ohio, United States, 54601
Akron City Hospital
Akron, Ohio, United States, 44304
Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford
Salem, Ohio, United States, 44460
Cancer Treatment Center
Wooster, Ohio, United States, 44691
CCOP - Columbus
Columbus, Ohio, United States, 43215
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195
Community Hospital of Springfield and Clark County
Springfield, Ohio, United States, 45505
Doctors Hospital at Ohio Health
Columbus, Ohio, United States, 43228
St. Rita's Medical Center
Lima, Ohio, United States, 45801
Genesis - Good Samaritan Hospital
Zanesville, Ohio, United States, 43701
Grady Memorial Hospital
Delaware, Ohio, United States, 43015
Grant Riverside Cancer Services
Columbus, Ohio, United States, 43215
Mercy Medical Center Oncology Unit
Springfield, Ohio, United States, 45504
Mount Carmel Cancer Services at Mount Carmel St. Ann's Hospital
Westerville, Ohio, United States, 43081
Mount Carmel West Hospital
Columbus, Ohio, United States, 43222
Radiation Oncology Center
Alliance, Ohio, United States, 44601
Riverside Methodist Hospital Cancer Care
Columbus, Ohio, United States, 43214
Fairfield Medical Center
Lancaster, Ohio, United States, 43130
Strecker Cancer Center at Marietta Memorial Hospital
Marietta, Ohio, United States, 45750
United States, Oregon
Kaiser Permanente Health Care - Portland
Portland, Oregon, United States, 97232
United States, Pennsylvania
Fox Chase-Temple Cancer Center
Philadelphia, Pennsylvania, United States, 19111-2497
York Cancer Center at Wellspan Health
York, Pennsylvania, United States, 17405
United States, South Carolina
Bon Secours St. Francis Health System
Greenville, South Carolina, United States, 29601
CCOP - Greenville
Greenville, South Carolina, United States, 29615
Greenville Hospital System Cancer Center
Greenville, South Carolina, United States, 29605
Hollings Cancer Center at Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Tennessee
University of Tennessee Cancer Institute at Methodist Central Hospital
Memphis, Tennessee, United States, 38163
United States, Virginia
Danville Regional Medical Center
Danville, Virginia, United States, 24541
Naval Medical Center - Portsmouth
Portsmouth, Virginia, United States, 23708-2197
United States, Washington
Cascade Cancer Center at Evergreen Hospital Medical Center
Kirkland, Washington, United States, 98033
CCOP - Virginia Mason Research Center
Seattle, Washington, United States, 98101
Central Washington Hospital
Wenatchee, Washington, United States, 98801
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98104
Olympic Medical Center
Port Angeles, Washington, United States, 98362
Harborview Medical Center
Seattle, Washington, United States, 98104
Olympic Hematology and Oncology
Bremerton, Washington, United States, 98310
Group Health Central Hospital
Seattle, Washington, United States, 98104
Rockwood Clinic Cancer Treatment Center
Spokane, Washington, United States, 99220
Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
Seattle, Washington, United States, 98114
University Cancer Center at University of Washington Medical Center
Seattle, Washington, United States, 98195
Valley Medical Center
Renton, Washington, United States, 98055
United States, Wisconsin
All Saints Cancer Center at All Saints Healthcare
Racine, Wisconsin, United States, 53405
Bay Area Cancer Care Center at Bay Area Medical Center
Marinette, Wisconsin, United States, 54143
St. Mary's Hospital Medical Center
Green Bay, Wisconsin, United States, 54303
St. Vincent Hospital Regional Cancer Center
Green Bay, Wisconsin, United States, 54301
Canada, Alberta
Cross Cancer Institute at University of Alberta
Edmonton, Alberta, Canada, T6G 1Z2
Tom Baker Cancer Centre - Calgary
Calgary, Alberta, Canada, T2V-4R6
Canada, British Columbia
British Columbia Cancer Agency - Centre for the Southern Interior
Kelowna, British Columbia, Canada, V1Y 5L3
British Columbia Cancer Agency - Vancouver Cancer Centre
Vancouver, British Columbia, Canada, V5Z 4E6
Fraser Valley Cancer Centre at British Columbia Cancer Agency
Surrey, British Columbia, Canada, V3V 1Z2
G. Steinhoff Clinical Research
Victoria, British Columbia, Canada, V8V 3N1
Prostate Centre at Vancouver General Hospital
Vancouver, British Columbia, Canada, V5Z 3J5
Canada, Manitoba
CancerCare Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, New Brunswick
Doctor Leon Richard Oncology Centre
Moncton, New Brunswick, Canada, E1C 8X3
Canada, Newfoundland and Labrador
Newfoundland Cancer Treatment and Research Foundation
St. Johns, Newfoundland and Labrador, Canada, A1B 3V6
Canada, Nova Scotia
Nova Scotia Cancer Centre at Queen Elizabeth II Health Sciences Centre
Halifax, Nova Scotia, Canada, B3H 1V7
Canada, Ontario
Cancer Centre of Southeastern Ontario at Kingston General Hospital
Kingston, Ontario, Canada, K7L 5P9
Carlo Fidani Peel Regional Cancer Centre at Credit Valley Hospital
Mississauga, Ontario, Canada, L5M 2N1
Hotel Dieu Health Sciences Hospital - Niagara
St. Catharines, Ontario, Canada, L2R 5K3
London Regional Cancer Program at London Health Sciences Centre
London, Ontario, Canada, N6A 4L6
Margaret and Charles Juravinski Cancer Centre
Hamilton, Ontario, Canada, L8V 5C2
Toronto Sunnybrook Regional Cancer Centre at Sunnybrook and Women's College Health Sciences Centre
Toronto, Ontario, Canada, M4N 3M5
Northwestern Ontario Regional Cancer Care at Thunder Bay Regional Health Sciences Centre
Thunder Bay, Ontario, Canada, P7B 6V4
Ottawa Hospital Regional Cancer Centre - General Campus
Ottawa, Ontario, Canada, K1H 8L6
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Northeastern Ontario Regional Cancer Centre
Sudbury, Ontario, Canada, P3E 5J1
Windsor Regional Cancer Centre at Windsor Regional Hospital
Windsor, Ontario, Canada, N8W 2X3
Canada, Quebec
Centre Hospitalier de l'Universite de Montreal
Montreal, Quebec, Canada, H2L-4M1
Centre Hospitalier Universitaire de Quebec
Quebec City, Quebec, Canada, G1R 2J6
CHUS-Hopital Fleurimont
Sherbrooke, Quebec, Canada, J1H 5N4
Maisonneuve-Rosemont Hospital
Montreal, Quebec, Canada, H1T 2M4
McGill Cancer Centre at McGill University
Montreal, Quebec, Canada, H2W 1S6
Canada, Saskatchewan
Allan Blair Cancer Centre at Pasqua Hospital
Regina, Saskatchewan, Canada, S4T 7T1
Saskatoon Cancer Centre at the University of Saskatchewan
Saskatoon, Saskatchewan, Canada, S7N 4H4
United Kingdom, England
Saint John Regional Hospital
Preston, England, United Kingdom, PR2 9HT

Sponsors and Collaborators

NCIC Clinical Trials Group

National Cancer Institute (NCI)

Southwest Oncology Group

Investigators

Study Chair:	Laurence H. Klotz, MD	Edmond Odette Cancer Centre at Sunnybrook
Study Chair:	Celestia S. Higano, MD	University of Washington

Study ID Numbers:	CDR0000066745, CAN-NCIC-PR7, SWOG-JPR7, ICR-CTSU-JPR7
Study First Received:	November 1, 1999
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00003653 History of Changes
Health Authority:	United States: Federal Government