Preoperative Radiation Therapy for High Risk Prostate Cancer

Study Overview
=================
Brief Summary
-----------------
This is a Phase I dose-escalation study of moderate dose radiation therapy prior to radical prostatectomy for patients with high-risk localized disease. Its hypothesis is that such treatment will be well tolerated with similar side effect profile as surgery alone. Patients in Groups 1 and 2 will receive 39.6 Gy and 45 Gy (at 1.8 Gy/fx), respectively, to the whole pelvis. Patients in Groups 3 and 4 will receive 45 Gy to the whole pelvis, followed by a boost to the prostate and periprostatic tissue, for total doses of 50.4 and 54 Gy, respectively. The patient will then undergo radical prostatectomy between 4-8 weeks after completion of radiation.

Official Title
-----------------
A Phase I Dose-Escalation Study of Preoperative Radiation Therapy Followed by Radical Prostatectomy in Patients With High Risk, Localized Carcinoma of the Prostate

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

Intervention / Treatment
-----------------
* Radiation: Radiation
* Procedure: Radical Prostatectomy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects must have biopsy-confirmed high-risk prostate cancer, defined as A. PSA > 20, B. Gleason Score (GS) >/= 8, and/or C. Clinical stage T3 disease per AJCC Staging Manual, 6th edition; or D. At least two out of three of the following: PSA 10-19.9, GS = 7, or clinical stage = T2b / T2c. a negative bone scan, be medically fit to undergo surgery as determined by treating urologist, age > 18, KPS must be >/= 80, no prior pelvic radiation therapy, chemotherapy, or androgen deprivation, no prior invasive malignancy, except non- melanomatous skin cancer unless disease free for a minimum of 5 years. Carcinoma in-situ of the bladder or head and neck region is permissible. Subjects must freely sign informed consent to enroll in the study. Exclusion Criteria: prior pelvic radiation therapy, chemotherapy, or androgen deprivation, prior invasive malignancy, except non- melanomatous skin cancer, carcinoma in-situ of the bladder or head and neck region, unless disease free for a minimum of 5 years. Metastatic disease as demonstrated by bone scan, CT scan or MRI of the pelvis, or chest x-ray. Pathologically documented positive pelvic lymph nodes. If Pre-operative CT scan or MRI (ordered at the discretion of the treating physicians) demonstrates lymph nodes which are suspicious for involvement, then biopsy must be undertaken and nodes proven negative before patient can enroll on this trial. Declared high-risk for anesthesia by attending anesthesiologist, cardiologist, or other physician. History of prior pelvic radiation therapy. History of androgen deprivation therapy or chemotherapy.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
Male

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

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

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Leve 1 Radiation<br>Subjects in Group 1 will receive 39.6 Gy (at 1.8 Gy/fx) to the whole pelvis. The subject will then undergo radical prostatectomy between 4-8 weeks after completion of radiation. | Radiation: Radiation<br>* Pre-operative Radiation to Prostate, SV, and Pelvic Lymph Nodes<br>Procedure: Radical Prostatectomy<br>* Patients will undergo evaluation by a surgeon for consideration of resection after completion of radiation therapy. If a surgical resection is possible, it is recommended that patients undergo surgery four to eight weeks after completion of radiation therapy. This surgical procedure will be performed by one of the standard accepted approaches.<br>|
| Experimental: Level 2 Radiation<br>Subjects in Group 2 will receive 45 Gy (at 1.8 Gy/fx) to the whole pelvis. The subject will then undergo radical prostatectomy between 4-8 weeks after completion of radiation. | Radiation: Radiation<br>* Pre-operative Radiation to Prostate, SV, and Pelvic Lymph Nodes<br>Procedure: Radical Prostatectomy<br>* Patients will undergo evaluation by a surgeon for consideration of resection after completion of radiation therapy. If a surgical resection is possible, it is recommended that patients undergo surgery four to eight weeks after completion of radiation therapy. This surgical procedure will be performed by one of the standard accepted approaches.<br>|
| Experimental: Level 3 Radiation<br>Subjects in Group 3 will receive 45 Gy to the whole pelvis, followed by a boost to the prostate and periprostatic tissue, for total doses of 50.4 Gy. The subject will then undergo radical prostatectomy between 4-8 weeks after completion of radiation. | Radiation: Radiation<br>* Pre-operative Radiation to Prostate, SV, and Pelvic Lymph Nodes<br>Procedure: Radical Prostatectomy<br>* Patients will undergo evaluation by a surgeon for consideration of resection after completion of radiation therapy. If a surgical resection is possible, it is recommended that patients undergo surgery four to eight weeks after completion of radiation therapy. This surgical procedure will be performed by one of the standard accepted approaches.<br>|
| Experimental: Level 4 Radiation<br>Subjects in Group 4 will receive 45 Gy to the whole pelvis, followed by a boost to the prostate and periprostatic tissue, for total doses of 54 Gy. The subject will then undergo radical prostatectomy between 4-8 weeks after completion of radiation. | Radiation: Radiation<br>* Pre-operative Radiation to Prostate, SV, and Pelvic Lymph Nodes<br>Procedure: Radical Prostatectomy<br>* Patients will undergo evaluation by a surgeon for consideration of resection after completion of radiation therapy. If a surgical resection is possible, it is recommended that patients undergo surgery four to eight weeks after completion of radiation therapy. This surgical procedure will be performed by one of the standard accepted approaches.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| post-operative morbidity |  | 30 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| continence |  | 1 year | 
| erectile function |  | 1 year | 
| biochemical recurrence |  | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
prostatectomy, radiation, neoadjuvant