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

This study has been completed.
Sponsor:
Collaborators:
Southwest Oncology Group
Information provided by (Responsible Party):
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00003653
First received: November 1, 1999
Last updated: January 10, 2013
Last verified: August 2012

November 1, 1999
January 10, 2013
January 1999
May 2010   (final data collection date for primary outcome measure)
Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00003653 on ClinicalTrials.gov Archive Site
  • Time to hormone resistance [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Quality of life by European Organization for Research of the Treatment of Cancer Quality of Life Questionnaire-C30+ (EORTC QLQ-C30+) trial specific checklist [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Serum cholesterol, high-density lipoprotein, and low-density lipoprotein levels [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Duration of treatment and non-treatment interval during intermittent androgen suppression arm only [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Time to testosterone recovery during intermittent androgen suppression arm only [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Time to recovery of potency during intermittent androgen suppression arm only [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
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

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Prostate Cancer
  • 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

  • Active Comparator: Intermittent Androgen Suppression
    Interventions:
    • Drug: bicalutamide
    • Drug: buserelin
    • Drug: cyproterone acetate
    • Drug: flutamide
    • Drug: goserelin
    • Drug: leuprolide acetate
    • Drug: nilutamide
  • Active Comparator: Continuous Androgen Suppression
    Interventions:
    • Drug: bicalutamide
    • Drug: buserelin
    • Drug: cyproterone acetate
    • Drug: flutamide
    • Drug: goserelin
    • Drug: leuprolide acetate
    • Drug: nilutamide

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1386
January 2013
May 2010   (final data collection date for primary outcome measure)

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
Male
16 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT00003653
PR7, CAN-NCIC-PR7, SWOG-JPR7, ICR-CTSU-JPR7, CDR0000066745
Yes
NCIC Clinical Trials Group
NCIC Clinical Trials Group
  • National Cancer Institute (NCI)
  • Southwest Oncology Group
Study Chair: Laurence H. Klotz, MD Edmond Odette Cancer Centre at Sunnybrook
Study Chair: Celestia S. Higano, MD University of Washington
NCIC Clinical Trials Group
August 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP