Androgen Deprivation Therapy in Treating Patients With Prostate Cancer

Study Overview
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Brief Summary
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RATIONALE: Androgens can cause the growth of prostate cancer cells. Androgen deprivation therapy may stop the adrenal glands from making androgens. PURPOSE: This randomized phase III trial is studying how well androgen deprivation therapy works in treating patients with prostate cancer.

Detailed Description
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OBJECTIVES: Primary Compare overall survival (with acceptable morbidity) of patients with prostate cancer treated with delayed vs immediate androgen deprivation therapy (ADT). Secondary Compare cancer-specific survival of patients treated with these regimens. Compare clinical progression in patients treated with these regimens. Compare time to first androgen independence in patients treated with these regimens. Compare complication rate incidence and timing (e.g., cord compression or pathological failure) in patients treated with these regimens. Compare treatment-related morbidity (including cognitive morbidity or osteoporosis) in patients treated with these regimens. Compare quality of life of patients treated with these regimens. Determine prognostic factors for progression in patients treated with delayed ADT. OUTLINE: This is a multicenter, randomized, controlled study. Patients in group 1 are stratified according to prior therapy (prostatectomy vs radiotherapy vs prostatectomy and radiotherapy), relapse-free interval (< 2 years vs ≥ 2 years), type of planned androgen deprivation therapy (ADT) (continuous vs intermittent), and participating center. Patients in group 2 are stratified according to type of planned ADT (continuous vs intermittent), disease type (localized vs metastatic), and participating center. Patients in both groups are randomized to 1 of 2 treatment arms. Arm I (delayed ADT): Beginning at least 2 years after study entry or after exhibiting evidence of significant disease progression*, patients receive either continuous ADT OR intermittent ADT comprising either bilateral orchiectomy OR luteinizing hormone-releasing hormone agonist with or without oral antiandrogen therapy. Arm II (immediate ADT): Beginning immediately after randomization, patients receive either continuous ADT OR intermittent ADT as in arm I. NOTE: *Patients in group 1 begin delayed ADT at least 2 years after study entry unless 1 of the following clinical criteria is present: prostate-specific antigen (PSA) doubling time of < 12 months with PSA ≥ 10 ng/mL OR PSA doubling time of ≤ 6 months based on 3 consecutive measurements obtained ≥ 2 months apart OR development of metastases or symptoms. Patients in group 2 begin delayed ADT at least 2 years after study entry unless 1 of the following clinical criteria is present: development of symptoms OR PSA ≥ 60 ng/mL OR PSA doubling time of ≤ 6 months based on 3 consecutive measurements obtained ≥ 2 months apart. After 9 months of ADT, all patients are assessed for response. Patients with PSA < 4 ng/mL may discontinue ADT. These patients are followed every 3 months. Treatment may be restarted when PSA is > 20 ng/mL OR PSA is > the PSA level at study entry OR at clinical progression. Quality of life is assessed at baseline, every 6 months for 2 years, and then annually for 3 years. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then periodically thereafter at the discretion of the principal investigator. PROJECTED ACCRUAL: A total of 300-2,000 patients will be accrued for this study within 2-5 years.

Official Title
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A Collaborative Randomized Phase III Trial: The Timing of Intervention With Androgen Deprivation in Prostate Cancer Patients With Rising PSA

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: antiandrogen therapy
* Drug: releasing hormone agonist therapy
* Procedure: orchiectomy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the prostate Prostate-specific antigen (PSA) relapse OR incurable disease diagnosed within the past 2 months AND meets criteria for either of the following groups: Group 1 In PSA relapse after definitive radical treatment (prostatectomy or radiotherapy), as evidenced by 1 the following: Post-prostatectomy PSA level ≥ 0.2 ng/mL At least 3 rising PSA levels (post-radiotherapy) obtained ≥ 1 month apart, with the last PSA obtained within the past 2 months No metastatic disease by bone scan or abdomino-pelvic CT scan Group 2 Not suitable for radical treatment at primary diagnosis Not planning to receive curative treatment Localized or metastatic disease No symptomatic disease requiring radiotherapy or immediate hormonal therapy No symptomatic disease requiring therapy PATIENT CHARACTERISTICS: Age Any age Performance status Not specified Life expectancy At least 5 years Hematopoietic Not specified Hepatic Not specified Renal Not specified Other No other significant comorbid condition that would limit life expectancy to < 5 years PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Not specified Endocrine therapy At least 12 months since prior androgen deprivation therapy (ADT) administered in the neoadjuvant or concurrent (with radiotherapy) setting (group 1) No prior ADT (group 2) Radiotherapy See Disease Characteristics See Endocrine therapy Surgery See Disease Characteristics Other No concurrent enrollment in TROG-96.01 or TROG-RADAR protocols
Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: antiandrogen therapy|nan|
|Drug: releasing hormone agonist therapy|nan|
|Procedure: orchiectomy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death from any cause at 8 years |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cancer specific survival |  |  | 
| Clinical progression |  |  | 
| Time to first androgen independence |  |  | 
| Complication rate incidence and timing (e.g., cord compression, pathological fracture) |  |  | 
| Treatment-related morbidity (including cognitive, osteoporosis) |  |  | 
| Prognostic factors for progression (delayed group) |  |  | 
| EORTC Quality of life - general QLQC30 and prostate module for Quality of life annually for 5 years |  |  | 
| CTC v3.0 Survival endpoints: actuarial analysis at eight years |  |  | 
| Morbidity continuously |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the prostate, stage I prostate cancer, stage IIB prostate cancer, stage IIA prostate cancer, stage III prostate cancer, stage IV prostate cancer, recurrent prostate cancer