Implant and External Radiation for Prostate Cancer With or Without Hormonal Therapy: A Prospective Randomized Trial

Study Overview
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Brief Summary
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Determine the role of androgen deprivation therapy in high risk patients receiving 45 Gy of pelvic radiotherapy plus a Pd-103 boost and the impact of the duration of ADT in hormonally-manipulated patients.

Detailed Description
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In calender year 2005, 220, 000 men will be diagnosed with prostate cancer and approximately 30,000 will subsequently die of metastatic disease. Although the vast majority of men will be diagnosed with clinically localized and potentially curable disease, the selection of one local modality over another remains a focus of significant controversy within the uro-oncology community. However, patients with higher risk features are most often managed with radiotherapeutic approaches to include androgen deprivation therapy. Prostate brachytherapy represents the ultimate-three dimensional conformal therapy and permits dose escalation far exceeding other modalities. Following permanent prostate brachytherapy with or without supplemental external beam radiation therapy, favorable long-term biochemical outcomes have been reported for patients with low, intermediate and high risk features with a morbidity profile that compares favorably with competing local modalities (1,2). Several prospective randomized trials have demonstrated that androgen deprivation therapy in conjunction with conventional doses of external beam radiation therapy (65-70 Gy)results in improvement in disease-free and overall survival in patients with locally advanced prostate cancer (3,4).

Official Title
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Implant and External Radiation for Prostate Cancer With or Without Hormonal Therapy: A Prospective Randomized Trial

Conditions
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Prostate Cancer

Intervention / Treatment
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* Radiation: External beam radiation
* Drug: Lupron
* Drug: Casodex


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: High risk patients - Two to three of the following: PSA 10-30 ng/mL, Gleason score greater than or equal to 6, clinical stage greater than or equal to T2c (2002 ACJJ). CT of the abdomen and pelvis and bone scan without evidence of metastases. An enzymatic prostatic acid phosphatase must be obtained prior to randomization. A serum testosterone must be obtained prior to initiation of androgen deprivation therapy. No prior pelvic external beam radiation therapy for prostate cancer or other malignancies. No prior androgen deprivation therapy. Minimum 5 year life expectancy. No other invasive cancer diagnosis other than non-melanoma skin cancer within the last 5 years. Exclusion Criteria: Exclusion criteria will be limited to patients who do not meet the above eligibility criteria.
Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: no hormones<br>All patients will receive a 5-week course of external beam radiation therapy to the pelvis and a Pd-103 brachytherapy implant with no hormones | Radiation: External beam radiation<br>* All patients will receive a 5-week course of external beam radiation therapy to the pelvis and a Pd-103 brachytherapy implant<br>|
| Active Comparator: 9 months of hormone therapy<br>All patients will receive a 5-week course of external beam radiation therapy to the pelvis and a Pd-103 brachytherapy implant with a 9 month course of hormone therapy | Radiation: External beam radiation<br>* All patients will receive a 5-week course of external beam radiation therapy to the pelvis and a Pd-103 brachytherapy implant<br>Drug: Lupron<br>* 9 months of an LHRH agonist and 4 months of an anti-androgen) is optimal for securing long-term biochemical control (a stable, non-rising PSA).<br>Drug: Casodex<br>* 9 months of an LHRH agonist and 4 months of an anti-androgen) is optimal for securing long-term biochemical control (a stable, non-rising PSA).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PSA 3 and 6 months following implantation then every 6 months. | PSA 3 and 6 months following implantation then every 6 months. | 3 and 6 months following implantation then every 6 months | 
| Serum testosterone levels at 3 and 6 months in hormonally manipulated patients. | Serum testosterone levels at 3 and 6 months in hormonally manipulated patients | 3 and 6 months | 
| Androgen deprivation therapy will not be reinitiated unless the post-treatment PSA exceeds 10 ng/mL or distant metastases are detected. | Androgen deprivation therapy will not be reinitiated unless the post-treatment PSA exceeds 10 ng/mL or distant metastases are detected. | as needed | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EPIC on 6 and 12 months and then annually. | EPIC on 6 and 12 months and then annually. | 6 and 12 months and then annually. | 
| Hormonally manipulated patients will obtain a DEXA scan. | Hormonally manipulated patients will obtain a DEXA scan. | as needed | 
| For documented osteoporosis, Zometa (4 mg IV over 15 minutes) every 3 months is recommended. | For documented osteoporosis, Zometa (4 mg IV over 15 minutes) every 3 months is recommended. | every 3 months is recommended. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Radiation therapy, Brachytherapy, Prostatic neoplasm