Randomized Trial of Adjuvant Hormonal Therapy in Surgically Treated Prostate Cancer Patients at High Risk for Recurrence

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Testosterone can stimulate the growth of prostate cancer cells. Hormone therapy using leuprolide and flutamide may fight prostate cancer by reducing the production of testosterone. It is not yet known whether receiving leuprolide and flutamide is more effective than receiving no further therapy. PURPOSE: Randomized phase III trial to determine the effectiveness of hormone therapy in treating patients who have stage I or stage II prostate cancer that is at high risk of recurrence and who have already undergone surgery.

Detailed Description
-----------------
OBJECTIVES: Determine the effect of one year of adjuvant hormonal ablation on disease-free survival at 5 years in node-negative radical prostatectomy patients at high risk for progression. Determine the effect of this treatment on the incidence of androgen independent prostate cancer and on disease specific and overall survival. Determine the impact of one year of total androgen ablation on quality of life and serum testosterone levels. Assess differences in quality of life between wives of patients in the androgen ablation condition compared to wives of patients in the control condition. Obtain blood samples from patients at high risk for failure post-prostatectomy to evaluate serum markers of prognosis. OUTLINE: This is a randomized study. Patients are randomized to one of two treatment arms. Arm I: Patients receive leuprolide intramuscularly once every 3 months and oral flutamide three times daily for 1 year. Arm II: Patients receive no initial treatment. Quality of life is assessed every 6 months for 5 years. Quality of life of wives/partners of patients is assessed every 6 months for two years. Patients are followed every 3 months for 1 year and then every 6 months for 4 years. PROJECTED ACCRUAL: A total of 496 patients (248 per treatment arm) will be accrued for this study within 3.5 years.

Official Title
-----------------
A Phase III Randomized Prospective Trial of Adjuvant Hormonal Therapy in Surgically Treated Prostate Cancer Patients at High Risk for Recurrence

Conditions
-----------------
Prostate Cancer

Intervention / Treatment
-----------------
* Drug: Flutamide
* Drug: Leuprolide Acetate


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Organ confined prostate cancer (stage T1-T2c) subsequent to clinical staging Radical prostatectomy and bilateral lymph node dissection performed Pathologic assessment of surgical specimens by MDACC pathologist High risk of clinical or biochemical failure post prostatectomy (must fulfill one of the following criteria): pathology; a) Gleason grade sum score greater than or equal to 8, b) Seminal vesicle involvement, c) Extraprostatic extension with positive surgical margins and Gleason greater than or equal to 7 Radical prostatectomy performed within 90 days of enrollment and serum PSA level < 0.1ng/ml Written informed consent Exclusion Criteria: Any evidence of metastatic disease confirmed prior to enrollment Inability to confirm pathologic risk factors or inadequate prostatectomy (see item 4.1.5). Hormonal ablation for greater than 3 months or radiotherapy for prostate cancer Failure to achieve prostate specific antigen level of less than 0.1ng/ml prior to enrollment in study Elevation of liver function tests 2x normal Contraindication to the use of LH-RH agonists or antiandrogens Active secondary malignancy (other than squamous or basal cell skin cancer) within five years prior to enrollment in study Any concomitant medical condition that would make it undesirable for the 7patient to participate in the trial or jeopardize compliance with the protocol
Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I - Leuprolide + Flutamide<br>Arm I: Patients receive leuprolide intramuscularly once every 3 months and oral flutamide three times daily for 1 year. | Drug: Flutamide<br>* 10.8 mg intramuscularly once every 3 months for 12 months<br>* Other names: Zoladex;Drug: Leuprolide Acetate<br>* 50 mg tablet orally daily for 12 months<br>* Other names: Bicalutamide;|
| No Intervention: Arm II - No Treatment<br>Arm II: Patients receive no initial treatment. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Disease Free Survival at 5 Years | To determine if one year of adjuvant hormonal ablation in node negative radical prostatectomy patients at high risk for progression will result in an improvement in disease-free survival at five years. | Beginning of the study up to 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage I prostate cancer, stage II prostate cancer