MRI Guided Radiation Therapy for the Treatment of High Risk Prostate Cancer

Study Overview
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Brief Summary
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This phase II trial tests whether magnetic resonance imaging (MRI)-guided hypofractionated radiation therapy works to reduce treatment time and side effects in patients with high risk prostate cancer. MRI-guided hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time directly to diseased tissue, reducing damage to healthy tissue. Using MRI-guided radiation therapy on areas of the prostate and pelvic lymph nodes may shorten overall treatment time compared to the longer standard of care therapy and may reduce the number and/or duration of side effects.

Detailed Description
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PRIMARY OBJECTIVE: I. Evaluate late grade 2+ genitourinary (GU) toxicity. SECONDARY OBJECTIVE: I. Evaluating acute GU and gastrointestinal (GI) toxicity, late GI toxicity, overall survival, prostate cancer specific survival, biochemical failure, and quality of life. OUTLINE: Patients undergo MRI-guided intensity-modulated radiation therapy (IMRT) on study and receive standard of care (SOC) antiandrogen therapy (ADT) throughout the trial. Patients may also undergo prostate specific membrane antigen (PSMA) positron emission tomography (PET), computed tomography (CT), MRI, and bone scans at screening and undergo collection of blood samples throughout the trial.

Official Title
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Phase 2 Study of Extreme Hypofractionation Including Pelvic Nodes for High Risk Prostate Cancer Using MgRT (MRI Guided Radiation Therapy)

Conditions
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Prostate Adenocarcinoma, Stage IIIB Prostate Cancer AJCC v8, Stage IIIC Prostate Cancer AJCC v8

Intervention / Treatment
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* Procedure: MRI-guided Intensity-Modulated Radiation Therapy
* Drug: Antiandrogen Therapy
* Procedure: PSMA PET Scan
* Procedure: Computed Tomography
* Procedure: Magnetic Resonance Imaging
* Procedure: Bone Scan
* Procedure: Biospecimen Collection
* Other: Quality-of-Life Assessment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: above 18 years Participants must be histologically proven, adenocarcinoma prostate Localized to the prostate without positive pelvic lymph node involvement No distant metastatic disease assessed by pretreatment PSMA PET or bone scan and CT scan High risk prostate cancer as defined by National Comprehensive Cancer Network (NCCN): Gleason score of 8- 10, clinical stage T3a or higher, or prostate specific antigen (PSA) > 20 ng/mL Ability to receive long term hormone therapy Karnofsky performance score (KPS) > 70 No prior history of therapeutic irradiation to pelvis Patient willing and reliable for follow-up and quality of life (QOL) English speaking/reading Exclusion Criteria: Evidence of distant or pelvic metastasis at any time since presentation Life expectancy < 2 years Previous radiation therapy (RT) to prostate or prostatectomy A previous trans-urethral resection of the prostate (TURP) Severe urinary symptoms or with severe International Prostate Symptom Score (IPSS) score despite being on hormonal therapy for 6 months which in the opinion of the physician precludes RT Patients with known obstructive symptoms with stricture Any contraindication to radiotherapy such as inflammatory bowel disease

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 (MRI-guided IMRT, ADT)<br>Patients undergo MRI-guided IMRT on study and receive SOC ADT throughout the trial. Patients may also undergo PSMA PET, CT, MRI, and bone scans at screening and undergo collection of blood samples throughout the trial. | Procedure: MRI-guided Intensity-Modulated Radiation Therapy<br>* Undergo MRI-guided IMRT<br>Drug: Antiandrogen Therapy<br>* Receive SOC ADT<br>* Other names: Hormone-Deprivation Therapy;Procedure: PSMA PET Scan<br>* Undergo PSMA PET scan<br>* Other names: PSMA-Positron emission tomography;Procedure: Computed Tomography<br>* Undergo CT<br>* Other names: Computerized axial tomography (procedure);Procedure: Magnetic Resonance Imaging<br>* Undergo MRI<br>* Other names: Magnetic resonance imaging (procedure);Procedure: Bone Scan<br>* Undergo bone scan<br>* Other names: Bone Scintigraphy;Procedure: Biospecimen Collection<br>* Undergo blood sample collection<br>* Other names: Specimen Collection;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of late grade 2+ genitourinary (GU) toxicity | Per Common Terminology Criteria for Adverse Events version 5.0 compared to rate of toxicity in POP-RT trial. Will be estimated for the entire sample that receives the intervention, treating death from any cause (other than treatment) as a competing risk and censoring subjects who drop out before experiencing toxicity at time of last follow-up. A point estimate of cumulative incidence at 1 year will be estimated from this curve along with a two-sided 90% confidence interval. If the upper bound of the interval is less than 20%, the null hypothesis will be rejected. | At 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of acute GU and gastrointestinal (GI) toxicity | Will be estimated using a binomial proportion and exact 95% confidence interval. | At baseline | 
| Incidence of acute GU and gastrointestinal (GI) toxicity | Will be estimated using a binomial proportion and exact 95% confidence interval. | At treatment completion, up to 10 days | 
| Incidence of acute GU and gastrointestinal (GI) toxicity | Will be estimated using a binomial proportion and exact 95% confidence interval. | every 3 months after treatment until 1 year | 
| Incidence of acute GU and gastrointestinal (GI) toxicity | Will be estimated using a binomial proportion and exact 95% confidence interval. | every 6 months beginning at year 2, assessed up to 4 years | 
| Incidence of late GI toxicity | Will be estimated using a binomial proportion and exact 95% confidence interval. | At baseline | 
| Incidence of late GI toxicity | Will be estimated using a binomial proportion and exact 95% confidence interval. | At treatment completion, up to 10 days | 
| Incidence of late GI toxicity | Will be estimated using a binomial proportion and exact 95% confidence interval. | every 3 months after treatment until 1 year | 
| Incidence of late GI toxicity | Will be estimated using a binomial proportion and exact 95% confidence interval. | every 6 months beginning at year 2, assessed up to 4 years | 
| Overall survival | Will be estimated using the Kaplan-Meier method. | At baseline | 
| Overall survival | Will be estimated using the Kaplan-Meier method. | At treatment completion, up to 10 days | 
| Overall survival | Will be estimated using the Kaplan-Meier method. | every 3 months after treatment until 1 year | 
| Overall survival | Will be estimated using the Kaplan-Meier method. | every 6 months beginning at year 2, assessed up to 4 years | 
| Prostate cancer specific survival | Will be estimated using the Kaplan-Meier method. | At baseline | 
| Prostate cancer specific survival | Will be estimated using the Kaplan-Meier method. | At treatment completion, up to 10 days | 
| Prostate cancer specific survival | Will be estimated using the Kaplan-Meier method. | every 3 months after treatment until 1 year | 
| Prostate cancer specific survival | Will be estimated using the Kaplan-Meier method. | every 6 months beginning at year 2, assessed up to 4 years | 
| Biochemical failure | Defined as prostate specific antigen nadir plus 2 ng/ml. Will be estimated using the Kaplan-Meier method. | At baseline | 
| Biochemical failure | Defined as prostate specific antigen nadir plus 2 ng/ml. Will be estimated using the Kaplan-Meier method. | At treatment completion, up to 10 days | 
| Biochemical failure | Defined as prostate specific antigen nadir plus 2 ng/ml. Will be estimated using the Kaplan-Meier method. | every 3 months after treatment until 1 year | 
| Biochemical failure | Defined as prostate specific antigen nadir plus 2 ng/ml. Will be estimated using the Kaplan-Meier method. | every 6 months beginning at year 2, assessed up to 4 years | 
| Quality of life measurement | Using patient reported outcome-expanded prostate cancer index composite. Will be summarized using descriptive statistics. | At baseline | 
| Quality of life measurement | Using patient reported outcome-expanded prostate cancer index composite. Will be summarized using descriptive statistics. | At treatment completion, up to 10 days | 
| Quality of life measurement | Using patient reported outcome-expanded prostate cancer index composite. Will be summarized using descriptive statistics. | every 3 months after treatment until 1 year | 
| Quality of life measurement | Using patient reported outcome-expanded prostate cancer index composite. Will be summarized using descriptive statistics. | every 6 months beginning at year 2, assessed up to 4 years |