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

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.

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