SWOG-9346, Hormone Therapy in Treating Men With Stage IV Prostate Cancer

Study Overview
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Brief Summary
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RATIONALE: Testosterone can stimulate the growth of prostate cancer cells. Hormone therapy may be effective treatment for prostate cancer. It is not yet known which regimen of hormone therapy is most effective for stage IV prostate cancer. PURPOSE: This randomized phase III trial is studying two different regimens of hormone therapy and comparing how well they work in treating men with stage IV prostate cancer.

Detailed Description
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OBJECTIVES: Primary Compare the survival of patients with metastatic stage IV prostate cancer responsive to combined androgen-deprivation therapy (CAD) treated with intermittent vs continuous CAD. Compare the effects of these treatment regimens on impotence, libido, and vitality/fatigue as well as the physical and emotional well-being of these patients. Secondary Compare general symptoms, role functioning, global perception of quality of life, and social functioning of patients treated with these regimens. Assess prostate-specific antigen (PSA) levels after continuous CAD administered before randomization and evaluate PSA changes throughout randomized treatment of these patients. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to SWOG performance status (0-1 vs 2), severity of disease (minimal vs extensive), and prior hormonal therapy (neoadjuvant hormonal therapy vs finasteride vs neither). Induction therapy: Patients receive combined androgen-deprivation (CAD) therapy comprising goserelin subcutaneously once a month and oral bicalutamide once daily for 8 courses (7 months). Consolidation therapy: Patients are randomized to 1 of 2 consolidation regimens. Arm I (continuous CAD therapy): Patients continue CAD therapy as in induction therapy. Treatment continues in the absence of disease progression. Arm II (intermittent CAD therapy): Patients undergo observation in the absence of rising prostate-specific antigen (PSA) or clinical symptoms of progressive disease. Patients with rising PSA or progressive disease begin CAD therapy as in induction therapy. Patients whose PSA normalizes after 8 courses return to observation. Patients whose PSA does not normalize after 8 courses continue CAD therapy. Quality of life is assessed before induction therapy, at 3 months (before consolidation therapy), and then at 9 and 15 months. Patients are followed every 6-12 months for at least 10 years. PROJECTED ACCRUAL: Approximately 1,500 patients will be accrued for this study.

Official Title
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Intermittent Androgen Deprivation in Patients With Stage D2 Prostate Cancer, Phase III

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: bicalutamide
* Drug: goserelin acetate
* Other: clinical observation


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed adenocarcinoma of the prostate Metastatic stage IV (stage D2) Any number of bone metastases by bone scan allowed Unequivocal visceral organ metastases (liver, brain, or lung) allowed No suspected second primary tumors unless metastases are histologically confirmed, including special stains (e.g., prostate specific antigen [PSA] and prostatic alkaline phosphatase [PAP]) For entry into late induction therapy: No more than 1 month from the beginning of antiandrogen therapy to the beginning of luteinizing hormone-releasing hormone (LHRH) agonist therapy No more than 6 months since initiation of current combined androgen-deprivation therapy (LHRH agonist and antiandrogen) The effectiveness of the current depot LHRH agonist would not extend beyond 8 months after initiation of combined androgen therapy PSA at least 5 ng/mL No acute spinal cord compression PATIENT CHARACTERISTICS: Age: Adult Performance status: SWOG 0-2 Hematopoietic: Not specified Hepatic: Not specified Renal: Not specified Other: Recovered from any major infection No active medical illness that would preclude study or limit survival No other malignancy within the past 5 years except: Adequately treated basal cell or squamous cell skin cancer Adequately treated carcinoma in situ of the bladder Adequately treated other superficial cancer PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent biological response modifier therapy Chemotherapy: No concurrent chemotherapy Endocrine therapy: See Disease Characteristics More than 1 year since any prior neoadjuvant or adjuvant hormonal therapy for a duration of no more than 4 months Single or combination therapy allowed More than 1 year since prior finasteride for prostate cancer for a duration of no more than 9 months (less than 6 months for benign prostatic hypertrophy) Prior or concurrent megestrol for hot flashes allowed No other concurrent hormonal therapy Radiotherapy: No concurrent radiotherapy other than palliation of painful bone metastases Surgery: No prior bilateral orchiectomy Recovered from any prior major surgery

Ages Eligible for Study
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Minimum Age: 18 Years

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
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Consolidation arm I<br>Patients continue CAD therapy comprising goserelin subcutaneously once a month and oral bicalutamide once daily. Treatment continues in the absence of disease progression. | Drug: bicalutamide<br>* Given orally<br>Drug: goserelin acetate<br>* Given subcutaneously<br>|
| Experimental: Consolidation arm II<br>Patients undergo observation in the absence of rising prostate-specific antigen (PSA) or clinical symptoms of progressive disease. Patients with rising PSA or progressive disease begin CAD therapy as in consolidation arm I. Patients whose PSA normalizes after 8 courses return to observation. Patients whose PSA does not normalize after 8 courses continue CAD therapy. | Drug: bicalutamide<br>* Given orally<br>Drug: goserelin acetate<br>* Given subcutaneously<br>Other: clinical observation<br>* Patients undergo observation in the absence of rising prostate-specific antigen (PSA) or clinical symptoms of progressive disease.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Non-inferiority test to determine if intermittent combined androgen deprivation (CAD) overall survival is not substantially worse than continuous CAD overall survival. Specifically, the trial is designed for a one-sided test of the hypothesis that the hazard ratio of intermittent CAD to continuous CAD is 1.2. The assumptions used to compute the trial size are an overall type I error rate of 0.05 and a type II error of 0.10 (power = 0.9). | Up to 15 years | 
| Physical Functioning as Measured by the SF-36 | This outcome was scored on a scale of 0 to 100, with higher scores indicating better functioning. Change from Baseline in SF-36 Score at 3 Months | 3 months | 
| Emotional Functioning as Measured by the SF-36 Mental Health Inventory | This outcome was scored on a scale of 0 to 100, with higher scores indicating better functioning. Change from Baseline in SF-36 Score at 3 Months | 3 months | 
| Erectile Dysfunction | This outcome was assessed by having patients report whether they had erectile dysfunction (a score of 1) or no erectile dysfunction (a score of 0). This analysis looks at change from Baseline to 3 Months. | 3 months | 
| High Libido | This outcome was assessed by having patients report whether their interest in sexual activities was very high, high, or moderate (a score of 1) or low or very low (a score of 0). This outcome measure is reporting a change from baseline in the percentage of participants with High Libido at 3 months. High Libido is defined as very high, high or moderate interest in sexual activities. | 3 months | 
| Vitality | This outcome was scored on a scale of 0 to 100, with higher scores indicating better functioning. This analysis looks at mean change from Baseline score to 3 Months. | 3 months | 

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