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

Trial Information

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

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.