Hypofractionated Whole Pelvic Radiotherapy of the Prostate

Study Overview
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Brief Summary
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This is a phase I feasibility study to evaluate the feasibility of hypofractionated whole pelvis radiotherapy in 35 patients with biopsy-proven intermediate- to high-risk prostate cancer as defined by NCCN risk criteria. Patients will have >15% risk of lymph node involvement as defined by the Roach equation 2/3(PSA)+10(Gleason Score-6). Day 0 of the study will be defined as the time of first LHRH/agonist/antagonist injection of hormone therapy. Radiation therapy should begin within 8 weeks (+/- 1 week) after the date of the first LHRH agonist/antagonist injection. Patients will be followed at 6 weeks and then every 3 months for the first 24 months after completion of radiotherapy in a similar schedule to usual standard of care. A history and physical, PSA, testosterone and EPIC-26 questionnaire will be collected at each visit. Any toxicity according to CTCAE v. 4.0 criteria will be documented. An interim analysis for evaluating acute toxicity (≤90 days) will be performed after the first follow-up visit of the20th patient enrolled on protocol. The trial will be terminated if >30% acute grade 2 or >5% grade 3 or greater toxicity is observed as a result of radiation treatment by CTCAE v. 4.0 criteria. Grade 2 toxicity is defined as a minimal, local or noninvasive intervention. Grade 3 toxicity is defined as a severe or medically significant but not immediately life-threatening event requiring hospitalization or prolongation of hospitalization. Previous studies have demonstrated approximately 30% and 5% incidence of Grade 2 and Grade 3 or greater toxicity, respectively, with conventionally fractionated radiotherapy followed by brachytherapy.

Official Title
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Phase I Feasibility Study of Accelerated Hypofractionated Whole Pelvic Radiotherapy for Patients With Intermediate-High Risk Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Radiation: Helical TomoTherapy (HT)
* Radiation: CyberKnife SBRT
* Radiation: Permanent Prostate Implant (PPI)
* Radiation: HDR brachytherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed intermediate- to high-risk prostate adenocarcinoma (T1c-T3b, PSA >10, and/or Gleason score ≥ 7) who have a greater than 15% risk of lymph node involvement as determined by the Roach equation. History/physical examination with digital rectal examination of the prostate within 8 weeks prior to registration Zubrod performance status 0-2 Age ≥18 years Ability to understand a written informed consent document, and the willingness to sign it Exclusion Criteria: Prior or concurrent invasive malignancy (except non-melanomatous skin cancer) or lymphomatous/hematogenous malignancy unless continually disease free for a minimum of 5 years. Evidence of distant metastases Regional lymph node involvement Previous radical surgery (prostatectomy) or cryosurgery for prostate cancer Previous pelvic irradiation, prostate brachytherapy Previous or concurrent cytotoxic chemotherapy for prostate cancer Patients with history of inflammatory bowel disease or major bowel surgery. Prior transurethral resection of the prostate (TURP) procedure.

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: Treatment<br>Step 1: Pelvic Lymph Node Irradiation Helical TomoTherapy (HT): 41.25 Gy in 15 fractions of 2.75 Gy each Step 2: Treat boost volume to prostate and seminal vesicles Acceptable treatment modalities: CyberKnife SBRT: 19 Gy in 2 fractions of 9.5 Gy each with SBRT Permanent prostate implant (PPI): 108 Gy for low dose rate PPI with I-125 90 Gy for low dose rate PPI with Pd-103 HDR brachytherapy: 15 Gy in one fraction for HDR | Radiation: Helical TomoTherapy (HT)<br> <br> Radiation: CyberKnife SBRT<br> <br> Radiation: Permanent Prostate Implant (PPI)<br> <br> Radiation: HDR brachytherapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity | Acute G3 or greater genitourinary or gastrointestinal toxicity as measured by CTCAE v.4 | 90 days post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Late Toxicity | G3 or greater genitourinary or gastrointestinal toxicity as measured by CTCAE v.4 | From 90 days post treatment until 36 months from start of therapy | 
| High-Related Quality of Life (HRQOL) | EPIC-26 Questionnaire | Baseline, week prior to RT, 6 weeks post treatment, and at least every 6 months for the first 2 years. | 
| PSA Complete Response (PSA-CR) | Via PSA laboratory with PSA level ≤0.3 | 120-127 days after initiation of therapy |