Prospective Evaluation of Hypofractionation Proton Beam Therapy With Concurrent Treatment of the Prostate and Pelvic Nodes for Clinically Localized, High Risk or Unfavorable Intermediate Risk Prostate Cancer

Study Overview
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Brief Summary
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The study is to examine a moderate hypofractionation regimen of proton beam therapy for high risk or unfavorable intermediate risk prostate cancer. The prostate and seminal vesicles are treated with 6750 centigray (RBE) in 25 fractions (i.e. 270 centigray/fraction), while the regional pelvic nodes receive 4500 centigray (RBE) in 25 fractions (i.e. 180 centigray/fraction) simultaneously. The overall treatment time is 5 weeks.

Detailed Description
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Proton beam therapy can provide a therapeutic gain by offering at least equivalent (or superior) tumor control while reducing the risk of radiation toxicity, in comparison with conventional photon-based external beam radiotherapy, given its dose-deposition characteristics. Currently the clinical target volume of proton beam for the treatment of prostate cancer has been mostly limited to the prostate and the seminal vesicles. There has been no study of proton beam therapy to treat both the primary tumor in the prostate and the regional pelvic nodes simultaneously using a moderate hypofractionation regimen. The study is a prospective, single-arm, clinical trial to evaluate a moderate hypofractionation regimen of proton beam therapy for high risk or unfavorable intermediate risk prostate cancer. The clinical target volumes of proton beam therapy include both the prostate/seminal vesicles and the regional pelvic nodes. The primary objective is to assess late grade ≥ 3 gastrointestinal (GI) and genitourinary (GU) toxicity. The secondary objectives are to evaluate late grade ≥ 2 GI and GU toxicity, acute grade ≥ 3 GI and GU toxicity, and disease-free survival including freedom from PSA (prostate specific antigen) relapse at 5 years. The study provides an avenue to examine the safety, efficacy, cost effectiveness, and convenience of a moderate hypofractionation regimen (5-week course) of proton beam therapy.

Official Title
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Prospective Evaluation of Hypofractionation Proton Beam Therapy With Concurrent Treatment of the Prostate and Pelvic Nodes for Clinically Localized, High Risk or Unfavorable Intermediate Risk Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Radiation: Hypofractionation Proton beam therapy with Concurrent Treatment of the Prostate and Pelvic Nodes


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male; Age ≥ 18 years. Histological confirmation of adenocarcinoma of the prostate within 6 months of study enrollment. Clinical stage T1-2 N0 M0, Gleason Score 7, Prostate Specific Antigen (PSA) 20-100 ng/mL, or Clinical stage Any T N0 M0, Gleason Score 8-10, PSA ≤ 100 ng/mL, or Clinical stage T3-4 N0 M0, any Gleason Score, PSA ≤ 100 ng/mL, or Clinical stage T1-2 N0 M0, Gleason Score 4+3, PSA 10-20 ng/mL Zubrod performance score (PS) ≤ 1 Total bilirubin, aspartate aminotransferase, alkaline phosphatase, and serum creatinine: < 2 x upper normal limit Signed informed consent. Exclusion Criteria: Any known nodal (N1) or distant metastasis (M1) Previous androgen deprivation therapy lasting more than 6 months History of inflammatory bowel disease Presence of a hip prosthesis Prior pelvic radiotherapy or prostatectomy Prior or concurrent antineoplastic agents (chemotherapy) Previous or concurrent malignancy other than non-melanoma skin cancer within 5 years of diagnosis of prostate cancer. Inability to start the protocol treatment within 1 month after study enrollment. Medical or psychiatric conditions that preclude informed decision-making or compliance with the protocol treatment or follow-up

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: Hypofractionation Proton beam therapy<br>Hypofractionation Proton beam therapy with Concurrent Treatment of the Prostate and Pelvic Nodes | Radiation: Hypofractionation Proton beam therapy with Concurrent Treatment of the Prostate and Pelvic Nodes<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Late Grade ≥ 3 Gastrointestinal (GI) and Genitourinary (GU) Toxicity of Interest, Using the CTCAE v4.0 | Toxicity will be defined as an adverse event possibly, probably, or definitely related to proton beam therapy. A late GI or GU toxicity will be defined as a GI or GU toxicity that occurs between 3 months and 2 years from the completion of proton beam therapy. All patients meeting the eligibility criteria who have signed a consent form and have begun treatment will be evaluable for late toxicity, with the exception of patients determined to be a major violation. | Between 3 months and 24 months post proton beam therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Late Grade ≥ 2 GI and GU Toxicity of Interest, Using the CTCAE v4.0 | Toxicity will be defined as an adverse event possibly, probably, or definitely related to proton beam therapy. A late GI or GU toxicity will be defined as a GI or GU toxicity that occurs between 3 months and 2 years from the completion of proton beam therapy. All patients meeting the eligibility criteria who have signed a consent form and have begun treatment will be evaluable for late toxicity, with the exception of patients determined to be a major violation | Between 3 months and 24 months post proton beam therapy | 
| Acute Grade ≥ 3 GI and GU Toxicity of Interest Within 3 Months Post Proton Beam Therapy, Using the CTCAE v4.0 | Toxicity will be defined as an adverse event possibly, probably, or definitely related to proton beam therapy. All patients meeting the eligibility criteria who have signed a consent form and have begun treatment will be evaluable for late toxicity, with the exception of patients determined to be a major violation | Within 3 months post proton beam therapy | 
| Disease-free Survival Including Freedom From PSA Relapse at 5 Years Post Proton Beam Therapy | Disease-free survival is defined as the time from registration until the time of the first occurrence of biochemical failure, local recurrence, regional recurrence, distant metastases, or death due to any cause. The distribution of disease-free survival will be estimated using the method of Kaplan-Meier. | 5 years post proton beam therapy | 
| Disease-specific Survival at 5 Years Post Proton Beam Therapy | Disease-free survival is defined as the time from registration until the time of the first occurrence of biochemical failure, local recurrence, regional recurrence, distant metastases, or death due to any cause. The distribution of disease-free survival will be estimated using the method of Kaplan-Meier. | 5 years post proton beam therapy |