Prostate Cancer
Conditions
Brief summary
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
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.
Interventions
RADIATIONExternal beam radiation therapy
Standard of care EBRT
RADIATIONProstate brachytherapy boost
Standard of care BTX
DRUGAndrogen deprivation therapy
Standard of care ADT
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.
Sponsors
University of Wisconsin, Madison
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SCREENING
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 6-36 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 ≤20 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Imaging markers for mid-treatment response | Mid-treatment (approximately 3 months into treatment) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Genomic signatures correlated with imaging response | Baseline and mid-treatment (approximately 3 months into treatment) | 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. |
| Establish a correlation between PET imaging response and pathologic response | Baseline and mid-treatment (approximately 3 months into treatment) | 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. |
| Establish a correlation between MRI imaging response and pathologic response | Baseline and mid-treatment (approximately 3 months into treatment) | 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. |
| Imaging and genomic markers for prostate specific antigen (PSA) recurrence. | Baseline, 3 months post therapy, every 6 months for 5 years | Determine if imaging and genomic markers that predict for mid-treatment pathologic response also predict PSA recurrence. |
| Evaluate blood-based biomarkers for treatment response. | Baseline and mid-treatment (approximately 3 months into treatment) | 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). |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJohn Floberg, MD, PhD
University of Wisconsin, Madison
Outcome results
None listed