Neoadjuvant Stereotactic Body Radiotherapy Prior to Radical Prostatectomy for High Risk Prostate Cancer

Study Overview
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Brief Summary
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This is a single-arm prospective non-randomized, non-blinded trial to assess the safety of neoadjuvant stereotactic body radiation therapy (SBRT) before surgery in high risk prostate cancer patients. Radiation therapy will be delivered over 5 treatment sessions for approximately 1.5 weeks total.

Official Title
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A Phase I Trial of Neoadjuvant Stereotactic Body Radiotherapy Prior to Radical Prostatectomy for High Risk Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Radiation: Stereotactic Body Radiation Therapy
* Procedure: Radical Prostatectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have biopsy-confirmed adenocarcinoma of the prostate. Subjects must have a negative bone scan. Subjects must have one of the following risk factors: PSA ≥20 and/or Gleason score ≥8 and/or Clinical or radiographic stage ≥T3a per AJCC (American Joint Committee on Cancer) 7th Edition Staging Manual and/or Radiographic pelvic lymph node positive disease and/or At least two out of four of the following: PSA (Prostate Specific Antigen) 10-19.9, GS (Gleason Score) = 3+4, clinical stage = T2b/T2c, ≥50% positive biopsy cores. Subjects must freely sign informed consent to enroll in the study. Subjects must be medically fit to undergo surgery determined by the PI. Age ≥ 18 KPS Karnofsky Performance Status (performance status is an attempt to quantify cancer patients' general well-being and activities of daily life, scores range from 0 to 100 where 100 represents perfect health and 0 represents death): ≥70. No prior invasive malignancy in the past 3-years, except non-melanomatous skin cancer unless disease free for a minimum of 2 years. Carcinoma in-situ of the bladder or head and neck region is permissible. Subjects must not have had prior pelvic radiation therapy, Subjects must not have had prior androgen deprivation therapy in the past 6 months. Exclusion Criteria: Metastatic disease as demonstrated by bone scan, CT scan or MRI (Magnetic Resonance Imaging) of the pelvis, or chest x-ray. Declared high-risk for anesthesia by attending anesthesiologist, cardiologist, or other physician. History of prior pelvic radiation therapy. History of androgen deprivation therapy within the past 6 months.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SBRT<br>Stereotactic Body Radiation Therapy (SBRT) will be delivered over 5 treatment sessions for approximately 1.5 weeks total. | Radiation: Stereotactic Body Radiation Therapy<br>* Delivered over 5 treatment sessions for approximately 1.5 weeks total.<br>Procedure: Radical Prostatectomy<br>* Open, laparoscopic, or robotic radical prostatectomy and pelvic lymph node dissection to remove the prostate, seminal vesicles, and pelvic lymph nodes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) of Neoadjuvant SBRT | The MTD is defined as the SBRT dose that with radical prostatectomy induces dose-limiting toxicity in 28% of subjects or less. | 6-week post-prostatectomy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Urinary Incontinence | Urinary incontinence will be scored according to Common Toxicity Criteria for Adverse Events (CTCAE) v.4.0 (Grade 1 = Occasional, Grade 2 = Spontaneous, pads indicated, Grade 3 = Intervention indicated) | up to one year post treatment | 
| Incidence of Urinary Stricture | Urinary stricture, according to Common Toxicity Criteria for Adverse Events (CTCAE) v.4.0 (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening, Grade 5 = death.) | up to one year post treatment | 
| Incidence of Urinary Bother | Urinary bother, according to Common Toxicity Criteria for Adverse Events (CTCAE) v.4.0 (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening, Grade 5 = death.) | up to one year post treatment | 
| Rectal Toxicity | Rectal Toxicity, according to Common Toxicity Criteria for Adverse Events (CTCAE) v.4.0 (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening, Grade 5 = death.) | up to one year post treatment | 
| Number of Patients with Positive Surgical Margins | Surgical specimens will be evaluated by the study pathologist to determine rate of margin positivity. | 4-10 weeks post radiation therapy | 
| Number of Patients with Extracapsular Extension | Surgical specimens will be evaluated by the study pathologist to determine rate of extracapsular extension. | 4-10 weeks post radiation therapy |