Imaging and Genomic Biomarkers to Predict Response in Prostate Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the imaging and gene expression biomarkers in prostate cancer. Participants have high-risk prostate cancer and have indicated they will undergo external beam radiation therapy, brachytherapy, and androgen deprivation therapy (EBRT+BTX+ADT). Participants can expect to be in this study for up to 5 years.

Detailed Description
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This is a pilot study to prospectively investigate potential predictive imaging and genomic biomarkers for patients with high-risk prostate cancer treated with standard of care EBRT + BTX + ADT. The primary imaging modalities that will be evaluated will be PSMA positron emission tomography (PET) and multi-parametric magnetic resonance imaging (MRI). Pre-treatment PET/MRI scans will also be obtained as part of standard of care prior to study enrollment. Response will be assessed on a mid-treatment PET/MRI scan obtained for research purposes after completion of EBRT but prior to brachytherapy boost. PET/CT (computerized tomography) may be used instead if PET/MRI is not technically possible. Imaging response will be compared to pathology from image-directed prostate biopsies taken at the time of the brachytherapy boost. The primary genomic marker that will be evaluated is a clinically available gene-expression array, Decipher, that will be obtained as part of standard of care prior to study enrollment.

Official Title
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Pilot Study to Identify Radiogenomic Biomarkers to Predict Early Treatment Response to Androgen Deprivation Therapy and Radiation Therapy in High Risk Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Radiation: External beam radiation therapy
* Radiation: Prostate brachytherapy boost
* Drug: Androgen deprivation therapy
* Diagnostic Test: Positron emission tomography (PET)/magnetic resonance imaging (MRI)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 Histologically confirmed adenocarcinoma of the prostate Cancer classified as high-risk or very high-risk by National Comprehensive Cancer Network (NCCN) criteria: Grade group ≥4, PSA >20, or primary tumor stage ≥T3a ECOG performance status 0-1 Agreed to undergo EBRT, high dose rate (HDR) brachytherapy boost, and 12-24 months of ADT as part of standard of care therapy prior to study enrollment Able to undergo a HDR brachytherapy implant: Pre-radiation IPSS score ≤15 with or without medical management; prostate ≤60 cc as measured by MRI or ultrasound; no prior trans-urethral resection of prostate (TURP); and, median lobe extending into the bladder <1 cm No prior or concurrent malignancy unless disease-free for at least 5 years Exclusion Criteria: Evidence of regional or distant metastatic disease on pre-treatment bone scan, pelvic MRI, and/or CT of the abdomen/pelvis Prior pelvic radiation therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Screening
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EBRT + BTX + ADT, PET and MRI<br>Standard of care EBRT + BTX + ADT, with mid-treatment PET and MRI (or PET and CT) scans for research. | Radiation: External beam radiation therapy<br>* Standard of care EBRT<br>Radiation: Prostate brachytherapy boost<br>* Standard of care BTX<br>Drug: Androgen deprivation therapy<br>* Standard of care ADT<br>Diagnostic Test: Positron emission tomography (PET)/magnetic resonance imaging (MRI)<br>* Pelvic PET scanning with tracer will take approximately 45 minutes. This will be followed by the injection of a contrast agent followed by whole body PET/MRI scanning which will take approximately 30 minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Imaging markers for mid-treatment response | Evaluate prostate specific membrane antigen (PSMA) PET/MRI for imaging biomarkers that predict mid-treatment response to ADT and EBRT to identify participants at risk for poor response to radiation therapy and ADT. | Mid-treatment (approximately 3 months into treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Genomic signatures correlated with imaging response | Determine if the Decipher and PORTOS genomic scores (high vs low) and basal/luminal genomic subtypes are correlated with change in PSMA standardized uptake value (SUV) pre-to-mid-treatment. | Baseline and mid-treatment (approximately 3 months into treatment) | 
| Establish a correlation between PET imaging response and pathologic response | PET images will be assessed for response using change in SUV in order to establish a correlation between imaging response and pathologic response to ADT and EBRT on a lesion-by-lesion basis. Pathologic response will be evaluated considering change in percent core involvement, prostate cancer epithelial/stromal (E/S) ratio, PSMA, CC3 and Ki67 expression. Concordance will be assessed using the Kappa statistic. | Baseline and mid-treatment (approximately 3 months into treatment) | 
| Establish a correlation between MRI imaging response and pathologic response | MR images will be assessed for response using change in apparent diffusion coefficient (ADC) in order to establish a correlation between imaging response and pathologic response to ADT and EBRT on a lesion-by-lesion basis. Pathologic response will be evaluated as described in Outcome 3. Concordance will be assessed using the Kappa statistic. | Baseline and mid-treatment (approximately 3 months into treatment) | 
| Imaging and genomic markers for prostate specific antigen (PSA) recurrence. | Determine if imaging and genomic markers that predict for mid-treatment pathologic response also predict PSA recurrence. | Baseline, 3 months post therapy, every 6 months for 5 years | 
| Evaluate blood-based biomarkers for treatment response. | Messenger RNA from circulating tumor cells (CTCs) will be extracted to determine if presence of androgen receptor variants and a neuroendocrine prostate cancer signature (a score based upon the expression of a set of genes) is correlated with pathologic response (determined as outlined in Outcome 3). | Baseline and mid-treatment (approximately 3 months into treatment) |