CT-guided Stereotactic Body Radiation Therapy and MRI-guided Stereotactic Body Radiation Therapy for Prostate Cancer, MIRAGE Study

Study Overview
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Brief Summary
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This phase III trial studies compares CT-guided stereotactic body radiation therapy and MRI-guided stereotactic body radiation therapy (SBRT) in treating prostate cancer. Image-guided SBRT is a standard treatment for prostate cancer, which combines imaging of the cancer within the body with the delivery of therapeutic radiation doses produced on a linear accelerator machine. Imaging modalities for image-guided SBRT can be either computed tomography imaging (CT), magnetic resonance imaging (MRI), or a combination of the two. This research is being done to help determine whether there are benefits to MRI-guidance over CT-guidance in patients who are receiving the same radiation dose by SBRT to treat prostate cancer.

Detailed Description
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PRIMARY OBJECTIVE: I. To determine whether (MRI)-guided stereotactic body radiotherapy (SBRT) improves acute physician-scored genitourinary (GU) toxicity when compared with standard computed tomography (CT)-guided SBRT for prostate cancer (PCa). SECONDARY OBJECTIVES: I. To determine whether there are differences in acute grade >= 2 gastrointestinal (GI) toxicity as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 scale, following MRI-guided SBRT versus CT-guided SBRT. II. To determine whether there are differences in 5-year cumulative incidences of late grade >= 2 GU and GI physician-reported toxicity, following MRI-guided SBRT versus CT-guided SBRT. III. To quantify the temporal changes in patient-reported quality of life (QOL) outcomes, as assessed by the Expanded Prostate Cancer Index-26 (EPIC-26), International Prostate Symptom Scores (IPSS), and Sexual Health Inventory for Men (SHIM) QOL indices, following MRI-guided SBRT. IV. To determine whether there are differences in 5-year biochemical recurrence-free survival (BCRFS) following MRI-guided SBRT. V. To observe the proportion of SBRT fractions for which on-line adaptive radiotherapy is required due to changes in organ-at-risk anatomy. OUTLINE: Patients are randomized to 1 of 2 groups. GROUP I: Patients undergo 5 fractions of CT-guided SBRT over 14 days in the absence of disease progression or unacceptable toxicity. GROUP II: Patients undergo 5 fractions of MRI-guided SBRT over 14 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 4 years, and then yearly thereafter.

Official Title
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Magnetic Resonance Imaging-Guided Stereotactic Body Radiotherapy for Prostate Cancer (Mirage): A Phase III Randomized Trial

Conditions
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Prostate Adenocarcinoma

Intervention / Treatment
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* Radiation: CT-guided Stereotactic Body Radiation Therapy
* Radiation: MRI-guided Stereotactic Body Radiation Therapy
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed, clinical localized adenocarcinoma of the prostate No evidence of disease beyond the prostate and/or seminal vesicles (i.e., no suspicious pelvic lymph nodes or presence of metastatic disease outside the pelvis) Staging workup as recommended by the National Comprehensive Cancer Network (NCCN) on the basis of risk grouping: Low risk: No staging workup required Favorable intermediate-risk: CT abdomen/pelvis if Memorial Sloan Kettering Cancer Center (MSKCC) nomogram predicts >10% probability of lymph node involvement Unfavorable intermediate-risk: technetium bone scan, CT abdomen/pelvis if MSKCC nomogram predicts >10% probability of lymph node involvement High-risk: technetium bone scan, CT abdomen/pelvis if MSKCC nomogram predicts >10% probability of lymph node involvement Advanced imaging studies (i.e. prostate-specific membrane antigen positron emission tomography [PSMA PET] and axumin scan) can supplant a bone scan if performed first Ability to understand, and willingness to sign, the written informed consent Exclusion Criteria: Patients with neuroendocrine or small cell carcinoma of the prostate Patients with any evidence of distant metastases. Note, evidence of lymphadenopathy below the level of the renal arteries can be deemed loco regional per the discretion of the investigator Prior cryosurgery, high intensity focused ultrasound (HIFU) or brachytherapy of the prostate Prior pelvic radiotherapy History of Crohn's disease, ulcerative colitis, or ataxia telangiectasia Contraindications to MRI, including: Electronic devices such as pacemakers, defibrillators, deep brain stimulators, cochlear implants; Metallic foreign body in the eye or aneurysm clips in the brain; Severe claustrophobia

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group I (CT-SBRT)<br>Patients undergo 5 fractions of CT-guided SBRT over 14 days in the absence of disease progression or unacceptable toxicity. | Radiation: CT-guided Stereotactic Body Radiation Therapy<br>* Undergo CT-guided SBRT<br>* Other names: CT-guided SBRT;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Group II (MRI-SBRT)<br>Patients undergo 5 fractions of MRI-guided SBRT over 14 days in the absence of disease progression or unacceptable toxicity. | Radiation: MRI-guided Stereotactic Body Radiation Therapy<br>* Undergo MRI-guided SBRT<br>* Other names: MRI-guided SBRT;Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of acute grade >= 2 genitourinary (GU) physician-reported toxicity | Will be assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 scale. | 90 days after stereotactic body radiation therapy (SBRT) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of acute grade >= 2 gastrointestinal (GI) toxicity | Will be assessed by the CTCAE version 4.03 scale and rates will be reported descriptively | 90 days after SBRT | 
| Incidences of late grade >= 2 GU toxicity | Will be assessed by the CTCAE version 4.03 scale and analyzed using a cumulative incidence framework. | Up to 5 years | 
| incidences of late grade >= 2 GI toxicity | Will be assessed by the CTCAE version 4.03 scale and analyzed using a cumulative incidence framework. | Up to 5 years | 
| Patient-reported quality of life (QOL) outcomes | For the Expanded Prostate Cancer Index- 26 (EPIC-26) instrument, these will be represented by changes from baseline in the urinary incontinence, urinary obstruction, bowel, sexual function, and hormone/vitality domains. Changes will be analyzed with respect to whether they represent minimally important differences. For the International Prostate Symptom Score (IPSS) and Sexual Health Inventory for Men (SHIM) instruments, the numerical change from baseline, as well as the raw score at any given timepoint, will be extracted. | Up 5 years | 
| Biochemical recurrence-free survival (BCRFS) | Will be estimated using the Kaplan-Meier method as well as descriptively (mean, standard deviation, median, first and third quartiles, minimum, maximum)., with biochemical recurrence (BCR) defined as serum PSA levels that are 2 ng/mL higher than the nadir PSA achieved after SBRT. | 5 years |