Stereotactic Body Radiation Therapy or Intensity-Modulated Radiation Therapy in Treating Patients With Stage IIA-B Prostate Cancer

Study Overview
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Brief Summary
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This randomized phase III trial studies how well stereotactic body radiation therapy works compared to intensity-modulated radiation therapy in treating patients with stage IIA-B prostate cancer. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Stereotactic body radiation therapy is a specialized radiation therapy that sends x-rays directly to the tumor using smaller doses over several days and may cause less damage to normal tissue. Stereotactic body radiation therapy may work better in treating patients with prostate cancer.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine whether stereotactic body radiation therapy (SBRT) can be shown to be superior to hypofractionated intensity-modulated radiation therapy (IMRT) in terms of genitourinary (GU) and gastrointestinal (GI) toxicity by having fewer patients that experience a minimal important decline (MID) in urinary irritation/obstructive and bowel Health Related Quality of Life (HRQOL) as measured by Expanded Prostate Cancer Index Composite (EPIC)-26 at 24 months post completion of therapy. SECONDARY OBJECTIVES: I. To determine if SBRT (5 fractions of 7.25 Gy) is superior to hypofractionated IMRT (28 fractions of 2.5 Gy) as measured by disease free survival (DFS). II. To determine whether SBRT can be shown to be superior to hypofractionated IMRT at 12 and 24 months post completion of therapy in terms of HRQOL by having fewer patients that experience a minimal important decline (MID) bowel (12 months only) sexual, hormonal, urinary irritation/obstructive (12 months only) and in urinary incontinence HRQOL as measured by EPIC-26. III. To determine if SBRT (5 fractions of 7.25 Gy) is superior to hypofractionated IMRT (28 fractions of 2.5 Gy) as measured by biochemical failure, overall survival, local failure, prostate cancer specific survival, and distant metastases. IV. To determine if prostate imaging-reporting and data system (PIRADS)version (v)2 = 4/5 disease is predictive for biochemical failure. TERTIARY OBJECTIVES: I. To determine whether a potentially more expensive therapy, SBRT, would be cost-effective than standard hypofractionated IMRT as measured by the European Quality of Life Five Dimension Five Level Scale Questionnaire (EQ-5D-5L). II. To determine if disease characteristics captured on MRI can be used to predict which patients will respond to SBRT versus hypofractionated IMRT. III. Collect specimens for future translational research analyses. OUTLINE: Patients are randomized into 1 of 2 arms. ARM I: Patients undergo IMRT once daily for 5 fractions per week for 28 fractions over less than 32 business days. ARM II: Patients undergo SBRT at least every other day for 2-3 fractions per week for 5 fractions over less than 12 business days. After completion of study treatment, patients are followed up every 6-12 months until death or study termination.

Official Title
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Phase III IGRT and SBRT vs IGRT and Hypofractionated IMRT for Localized Intermediate Risk Prostate Cancer

Conditions
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Stage II Prostate Adenocarcinoma

Intervention / Treatment
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* Radiation: Intensity-Modulated Radiation Therapy (IMRT)
* Radiation: Stereotactic Body Radiation Therapy (SBRT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previously untreated (no local therapy such as surgery, radiation cryotherapy, HIFU, etc.) localized adenocarcinoma of the prostate with the following clinical findings: Clinical stage by digital rectal exam of either T1c or T2a/b (limited to one side of the gland); (American Joint Committee on Cancer [AJCC], version 7) or cT1a-c or 2a or 2b, Stages T1a-T1b are eligible if patient underwent transurethral prostatic resection (TURP), The patient must meet one of the following 3 criteria: 1) Gleason score must be Gleason 7(3+4) with a PSA < 20 ng/mL, or 2) Gleason 6(3+3) with a PSA > 10 ng/mL and < 20 ng/mL which is considered intermediate risk and eligible for the study. (AJCC, version 7) or 3) Group Grade 1 with a PSA > 10 ng/mL and < 20 ng/mL or 2 with a PSA < 20 ng/mL. If patient is receiving a 5-alpha reductase inhibitor at the time of enrollment the baseline PSA value may be double the initial value and the medication should be discontinued but a washout period is not required to eligible, a PSA drawn while still on the medicine must be: < 10 ng/mL if Gleason 7(3+4) (Note: This patient would be on stratification level 1 if PSA < 5 ng/mL and stratification level 2 if less than 10 ng/mL). > 5 ng/mL and less than 10 ng/mL for Gleason 6(3+3) (Note: This patients would be on stratification level 3). The prostate volume must be < 70 cc as reported at time of biopsy or by separate measure with ultrasound or other imaging modalities including magnetic resonance imaging (MRI) or computed tomography (CT) scan Patients in active surveillance who elect to be treated are eligible if they meet protocol requirements History and physical including a digital rectal exam 60 days prior to registration Eastern Cooperative Oncology Group (ECOG) performance status 0-1 60 days prior to registration MRI of the prostate and pelvis (per institutional SOC - should be compliant with PIRADSv2.1 guidelines) within 1 year prior to registration Bone scan or sodium fluoride positron emission tomography (PET) scan within 120 days prior to registration Charlson modified co-morbidity score =< 4 for patients under 60 and =< 5 for patients 60 and over 21 days prior to registration International prostate symptom score (IPSS) of < 15 21 days prior to registration The patient must provide study-specific informed consent prior to study entry Willingness and ability to complete the Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire Completion of all items of the EPIC-26 which will be data entered at registration 60 days prior to registration Only English, Spanish, and French-speaking patients are eligible to participate Exclusion Criteria: Definitive clinical or radiologic evidence of metastatic disease; no nodal involvement or evidence of metastatic disease allowed as defined by screening of the pelvis and a bone scan or sodium fluoride PET scan Definitive T3 disease on MRI Prior or current invasive malignancy with current evidence of active disease within the past 2 years Exceptions: Non-melanomatous skin cancer, carcinoma in situ of the male breast, penis, oral cavity, or stage Ta of the bladder, or stage I completely resected melanoma. Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable; must be off treatment for at least 3 years Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields The use of hormonal therapy is not allowed; if the patient in on a 5-alpha reductase inhibitor, then they should be stopped prior to treatment once enrolled onto the study; no washout period is required for this study to participate Severe, active co-morbidity defined as follows: Human immunodeficiency virus (HIV) positive with CD4 count < 200 cells/microliter; Note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count >= 200 cells/microliter within 30 days prior to registration; Note also that HIV testing is not required for eligibility for this protocol Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol; (patients on Coumadin or other blood thinning agents are eligible for this study) Contraindication to MRI Cardiac pacemaker or defibrillator Surgically implanted electrical devices such as spinal stimulation devices or intracranial stimulation devices, cochlear implants, the presence of metallic foreign bodies in the orbits, and incompatible old mechanical heart valves and aneurysm clips

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intensity-Modulated Radiation Therapy (IMRT)<br>Patients undergo Intensity-Modulated Radiation Therapy (IMRT) once daily 5 fractions per week for 28 fractions over less than 32 business days. | Radiation: Intensity-Modulated Radiation Therapy (IMRT)<br>* Undergo IMRT<br>* Other names: Intensity-Modulated Radiotherapy;|
| Experimental: Stereotactic Body Radiation Therapy (SBRT)<br>Patients undergo Stereotactic Body Radiation Therapy (SBRT) at least every other day for 2-3 fractions per week for 5 fractions over less than 12 business days. | Radiation: Stereotactic Body Radiation Therapy (SBRT)<br>* Undergo SBRT<br>* Other names: stereotactic body radiation therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Patients-Reported Gastrointestinal and Genitourinary Toxicity | Will be measured by Expanded Prostate Cancer Index Composite-(EPIC) 26 bowel and urinary irritation domains. Will be compared between treatment arms using a test of proportions with two-sided significance level of 0.05. | Up to 2 years | 
| Disease Free Survival | Will be estimated using the Kaplan-Meier method and treatment arms compared using the stratified log-rank test. | Time to biochemical failure (Phoenix definition), local failure, regional failure, distant metastasis, or death from any cause, assessed up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochemical Failure | Will be assessed by Phoenix definition. | yearsFrom the date of randomization to the date of biochemical failure, date of precluding death, or last known follow-up, assessed up to 5 years. | 
| Distant Metastasis | Will be assessed. | From the time of randomization to the date of distant metastasis, date of precluding death, or last known follow-up date , assessed for up to 5 years | 
| Health Related Quality of Life | Will be measured by EPIC-26 urinary incontinence, sexual, and hormonal domains. | Up to 2 years | 
| Incidence of adverse events (AEs) | Will be assessed by Common Terminology Criteria for Adverse Events version 4. Counts of all AEs by grade will be provided by treatment arm. Counts and frequencies will be provided for the worst grade AE experienced by the patient by treatment arm. The number of patients with at least 1 grade 3 or higher AE will be compared between the treatment arms. A comparison between treatment arms of grade 3 and higher genitourinary (GU) and gastrointestinal (GI) events related to treatment (separately) will also be tested. There are 5 pre-specified AEs, dysuria, hematuria, incontinence, rectal bleeding, | Up to 2 years | 
| Local Failure | Will be assessed. | From the time of randomization to the date of local failure, date of precluding death, or last known follow-up date, assessed for up to 5 years | 
| Overall Survival | Will be estimated using the Kaplan-Meier method and treatment arms compared using the stratified log-rank test. | From the date of randomization to the date of death or last known follow-up date, assessed up to 5 years | 
| Presence of Prostate Imaging-Reporting and Data System version (PIRADSv) 2 = 4/5 disease | Will be assessed by magnetic resonance imaging (MRI). | Baseline | 
| Prostate Cancer Specific Survival | Will be assessed. | yearsFrom the date of randomization to the date of prostate cancer death, date of precluding death, or last known follow-up date, assessed up to 5 years | 
| Regional Failure | Will be assessed. | From the time of randomization to the date of local failure, date of precluding death, or last known follow-up date, assessed for up to 5 years |