Hormone Therapy in Treating Patients With Rising PSA Levels Following Radiation Therapy for Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): bicalutamide; buserelin; cyproterone acetate; flutamide; goserelin; leuprolide acetate; nilutamide
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): 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; 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; 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; 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; 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; 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; 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
Intervention MeSH terms: Leuprolide; Goserelin; Flutamide; Bicalutamide; Cyproterone Acetate; Nilutamide; Buserelin; Cyproterone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: adenocarcinoma of the prostate; recurrent prostate cancer