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

NCIC Clinical Trials Group

Status and phase: Completed; Phase 3

Conditions: Prostate Cancer

Treatments: Drug: bicalutamide; Drug: nilutamide; Drug: cyproterone acetate; Drug: buserelin; Drug: leuprolide acetate; Drug: flutamide; Drug: goserelin

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00003653

CAN-NCIC-PR7 (Other Identifier)

SWOG-JPR7 (Other Identifier)

ICR-CTSU-JPR7 (Other Identifier)

CDR0000066745 (Other Identifier)

PR7

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1,386 patients

Sex: Male

Ages: 16 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,386 participants in 2 patient groups

Intermittent Androgen Suppression

Active Comparator group

Treatment:

Drug: buserelin

Drug: bicalutamide

Drug: leuprolide acetate

Drug: goserelin

Drug: nilutamide

Drug: flutamide

Drug: cyproterone acetate

Continuous Androgen Suppression

Active Comparator group

Treatment:

Drug: buserelin

Drug: bicalutamide

Drug: leuprolide acetate

Drug: goserelin

Drug: nilutamide

Drug: flutamide

Drug: cyproterone acetate