NCT00003653

Hormone Therapy in Treating Patients With Rising PSA Levels Following Radiation Therapy for Prostate Cancer

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

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1,386 (actual)
• Sponsor: NCIC Clinical Trials Group · Network
• Sex: Male
• Age: 16 Years – 120 Years
• Healthy volunteers: Not accepted

Summary

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.

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.

Conditions

• Prostate Cancer

Interventions

Type	Name	Description
DRUG	bicalutamide	Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment. Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented
DRUG	buserelin	Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment. Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented
DRUG	cyproterone acetate	Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment. Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented
DRUG	flutamide	Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment. Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented
DRUG	goserelin	Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment. Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented
DRUG	leuprolide acetate	Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment. Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented
DRUG	nilutamide	Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment. Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented

Timeline

• Start date: 1999-01-05
• Primary completion: 2010-10-04
• Completion: 2013-01-10
• First posted: 2003-01-27
• Last updated: 2021-06-23

Locations

29 sites across 1 country: Canada