Early Compared With Delayed Hormone Therapy in Treating Patients With Nonmetastatic Prostate Cancer

Study Overview
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Brief Summary
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Objectives I. Compare, in a randomized Phase III multi-institutional setting, symptom-free survival time of patients with asymptomatic carcinoma of the prostate (T0-4, N0-2, M0) not suited for local curative treatment who are randomly assigned to immediate vs. delayed endocrine intervention (orchiectomy or luteinizing hormone releasing hormone (LHRH) agonist therapy). II. Compare the overall survival of these two groups of patients. III. Compare the time to first evidence of distant progression (N4 or M1) of these two treatment groups. IV. Evaluate the prognostic significance of pretreatment laboratory data and monitor these parameters following endocrine therapy. V. Study the prognosis of various sub-groups of patients stratified according to performance status, local tumor extent, nodal status, and choice of endocrine treatment.

Official Title
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Phase III Comparison of Early vs Delayed Endocrine Manipulation (Orchiectomy or LHRH Agonist Therapy) in Previously Untreated Patients With Nonmetastatic Asymptomatic Carcinoma of the Prostate

Conditions
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Neoplasm, Prostate

Intervention / Treatment
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* Procedure: Immediate Orchiectomy or depot LHRH
* Procedure: Delayed Orchiectomy or depot LHRH


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically proven, newly diagnosed asymptomatic (with the exception of voiding disturbances) carcinoma of the prostate T0-4 N0-2 M0 which is not suitable for local treatment with curative intent (radical prostatectomy, radiation therapy). All T stages are acceptable (UICC 1982). The stage is determined by rectal palpation. Patients with regional lymph node metastases smaller than 5 cm (N0-2), determined either by CT or ultrasonography, preferable with cytologic confirmation. Life expectancy of at least six months. WHO performance status score 0-1. Informed consent. Patients must be prepared to undergo an orchiectomy or continuous treatment with a depot LHRH analogue. Continuous follow-up until death if possible. Exclusion Criteria: Other malignancies diagnosed during the last 10 years, apart from treated basal cell carcinoma of the skin. Prostate cancer known for longer than one month before entering the study. Pain caused by the prostate cancer or its metastases. Any previous treatment for prostate cancer (radical prostatectomy, radiation therapy, endocrine treatment, etc.) Note: TUR-P for voiding disturbances is allowed at any time and is not an exclusion criterion. Patients with ureteric obstruction caused by local infiltration of prostatic cancer and other evidence of locally advanced disease which could cause fatal complications if untreated (e.g. rectal stenosis, thrombosis of pelvic veins). Patients with palpable or juxtaregional lymph node metastasis (paraaortic, supraclavicular, inguinal, N3-4). Patients with evidence of distant metastases (bone, lung, liver). Age over 80 years. Performance status WHO score 2, 3 and 4 (any reason). Patient who refuses orchiectomy or longterm subcutaneous implants of LHRH analogue in two monthly intervals. Expected difficulties with follow-up for any reason.

Ages Eligible for Study
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Maximum Age: 80 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: Immediate Endocrine Therapy<br>Immediate Endocrine Therapy. Orchiectomy or LHRH Agonist Therapy plus (initially) Antiandrogen Therapy. Buserelin (BSRL); Cyproterone acetate (Androcur) (CPTR), Cyproterone acetate (Androcur)(NSC-81430). Treatment initiated within 1 month of randomization. | Procedure: Immediate Orchiectomy or depot LHRH<br> <br> |
| Experimental: Delayed Endocrine Therapy<br>Orchiectomy or LHRH Therapy plus (initially) Antiandrogen Therapy. BSRL; CPTR. Treatment delayed until onset of symptoms. | Procedure: Delayed Orchiectomy or depot LHRH<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 13 years from first patient in | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall symptom free survival time |  | 13 years from first patient in | 
| Time until first evidence of distant progression |  | 13 years from first patient in | 
| Prognostic importance of pretreatment laboratory data | prostate cancer mortality and overall mortality according to pretreatment laboratory data | 13 years from first patient in | 
| Prognosis of particular sub-groups | prostate cancer mortality and overall mortality according to particular sub-groups (following stratification factors): performance status (0 vs 1), the local tumor extent (T0-2 vs T3-4), nodal status (N0 vs N1-2), the choice of hormonal therapy. | 13 years from first patient in | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Malignant Neoplasm of Prostate, Tumor-node-metastasis (TNM) Staging Regional Lymph Nodes (N0-2), Not suitable for local treatment with curative intent