Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Related Publications
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Closed 16 and over NCI CAN-NCIC-PR7 SWOG-JPR7, ICR-CTSU-JPR7, JPR7, NCT00003653, PR7

Special Category: CTSU trial

Objectives

1. 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).
2. Compare the time to the development of hormone resistance in patients treated with these regimens.
3. Compare the quality of life of patients treated with these regimens.
4. 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.
5. 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.

Entry 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

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

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

Expected Enrollment

A total of 1,386 patients will be accrued for this study within 7 years.

Outcomes

Overall survival

Time to hormone resistance
Quality of life by European Organization for Research of the Treatment of Cancer Quality of Life Questionnaire-C30+ (EORTC QLQ-C30+) trial specific checklist
Serum cholesterol, high-density lipoprotein, and low-density lipoprotein levels
Duration of treatment and non-treatment interval during intermittent androgen suppression arm only
Time to testosterone recovery during intermittent androgen suppression arm only
Time to recovery of potency during intermittent androgen suppression arm only

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.

Klotz L, Correia A, Zhang W: The relationship between the androgen receptor CAG repeat polymorphism length and the response to intermittent androgen suppression therapy for advanced prostate cancer. Prostate Cancer Prostatic Dis 8 (2): 179-83, 2005.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

NCIC-Clinical Trials Group

Laurence Klotz, MD, Protocol chair		Ph: 416-480-4673

Southwest Oncology Group

Celestia Higano, MD, Protocol chair		Ph: 206-288-2048

Registry Information
Official Title		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 Start Date		1999-01-05
Registered in ClinicalTrials.gov		NCT00003653
Date Submitted to PDQ		1998-11-05
Information Last Verified		2006-11-06
NCI Grant/Contract Number		CA77202, CA77202