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:	NCIC Clinical Trials Group
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:	Allocation: Randomized Control: Active Control Primary Purpose: Treatment
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 NCIC Clinical Trials Group:

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

Show 153 Study Locations

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

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Klotz L, Correia A, Zhang W. The relationship between the androgen receptor CAG repeat polymorphism length and the response to intermittent androgen suppression therapy for advanced prostate cancer. Prostate Cancer Prostatic Dis. 2005 Apr 5; [Epub ahead of print]

Study ID Numbers:	CDR0000066745, CAN-NCIC-PR7, SWOG-JPR7, ICR-CTSU-JPR7
Study First Received:	November 1, 1999
Last Updated:	March 5, 2010
ClinicalTrials.gov Identifier:	NCT00003653 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by NCIC Clinical Trials Group:

adenocarcinoma of the prostate
recurrent prostate cancer

Additional relevant MeSH terms:

Buserelin
Prostatic Diseases
Genital Neoplasms, Male
Contraceptive Agents
Antineoplastic Agents
Hormone Antagonists
Physiological Effects of Drugs
Cyproterone
Hormones, Hormone Substitutes, and Hormone Antagonists
Urogenital Neoplasms
Reproductive Control Agents
Contraceptive Agents, Male
Flutamide
Neoplasms by Site
Leuprolide

Therapeutic Uses
Diane
Antineoplastic Agents, Hormonal
Nilutamide
Cyproterone Acetate
Goserelin
Genital Diseases, Male
Pharmacologic Actions
Neoplasms
Androgen Antagonists
Fertility Agents, Female
Fertility Agents
Bicalutamide
Prostatic Neoplasms

ClinicalTrials.gov processed this record on March 18, 2010