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
16 Years
N/A
Male
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Overall survival
Outcome Time Frame:
2 years
Safety Issue:
No
Principal Investigator
Laurence H. Klotz, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Edmond Odette Cancer Centre at Sunnybrook
Authority:
Canada: Health Canada
Study ID:
PR7
NCT ID:
NCT00003653
Start Date:
January 1999
Completion Date:
January 2013
Related Keywords:
- Prostate Cancer
- adenocarcinoma of the prostate
- recurrent prostate cancer
- Prostatic Neoplasms
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