Evaluation of PSMA-based PET as an Imaging Biomarker in Prostate Cancer

Study Overview
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Brief Summary
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This research is being done to see if an investigational radioactive imaging agent (radiotracer) called 18F-DCFPyL can help us find prostate cancer at its original site in the prostate gland and in distant sites (bone, lymph nodes) in men diagnosed with prostate cancer before surgery.

Detailed Description
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The investigators propose to evaluate the feasibility of using a novel small molecule PET radiotracer, DCFPyL to target prostate cancer prostate-specific membrane antigen (PSMA). PSMA is a well studied cell surface marker of prostate cancer with increased expression associated with higher tumor grade and advanced metastatic tumors. More specifically it is associated with a higher Gleason score and there is evidence it can serve as a potential marker for prostate tumor carcinogenesis, progression and as a AR signaling surrogate marker of ADT response. This small molecule PET radiotracer specifically targeting an important prostate specific marker of AR signaling dynamics following ADT, tumor progression and metastatic potential warrants validation as an in-vivo non-invasive imaging biomarker for PSMA expression and prostate cancer detection.

Official Title
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Evaluation of PSMA-based PET as an Imaging Biomarker of Androgen Receptor Signaling in High-Risk Localized and Locally Advanced Prostate Cancer

Conditions
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Advanced Prostate Cancer

Intervention / Treatment
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* Drug: Pelvic DCFPyL PET-MRI fusion or PET/MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men 18 years of age or greater with recently diagnosed prostate cancer with planned radiation and ADT. Key inclusion criteria (the entire list of inclusion and exclusion criteria will appear later in section 4 of the protocol) Newly diagnosed prostate cancer pathologically proven by prostate biopsy Prostate biopsy histology grade ≥ Gleason 8-10 Patients considered as candidates for and medically fit to undergo radiation and ADT At least 10 days after most recent prostate biopsy Exclusion Criteria: Prior pelvic external beam radiation therapy or brachytherapy Chemotherapy for prostate cancer Hormone deprivation therapy Investigational therapy for prostate cancer Hemorrhagic cystitis or active prostatitis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 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: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DCFPyL PET-MRI fusion or PET/MRI<br>Pelvic DCFPyL PET-MRI fusion or PET/MRI compared before and after 2-3 months of ADT Pelvic DCFPyL PET-MRI fusion or PET/MRI compared before and after 2-3 months | Drug: Pelvic DCFPyL PET-MRI fusion or PET/MRI<br>* Pelvic DCFPyL PET-MRI fusion or PET/MRI compared before and after 2-3 months of ADT Pelvic DCFPyL PET-MRI fusion or PET/MRI compared before and after 2-3 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate differences | To compare the detection , sextant localization and response of DCFPyL PET-MRI fusion or PET/MRI before and after 2-3 months of ADT in men with biopsy-positive high-risk localized or locally advanced prostate cancer. | baseline and after 2-3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarker changes | To compare DCFPyL PET-MRI fusion or PET/MRI uptake in prostate cancer (quantified as per sextant SUVmax, SUVavg, metabolic tumor volume, total lesion DCFPyL uptake, DCFPyL uptake rate) as a reliable non-invasive imaging biomarker of PSMA expression following ADT as determined by qualitative and quantitative MRI-guided prostate biopsy core tissue immunohistochemical analysis. DCFPyL uptake will also be compared to other prostate cancer relevant marker expression levels (PSA, Ki-67, TMPRSS2-ERG) by immunohistochemical analysis. | Baseline and at 2=3 months | 
| Metabolic tumor uptake changes | To compare DCFPyL PET-MRI fusion or PET/MRI uptake in primary prostate cancer (quantified as per sextant SUVmax, SUVavg, metabolic tumor volume, total lesion DCFPyL uptake, DCFPyL uptake rate) following ADT with standard clinical prognostic markers (PSA, Gleason score, clinical stage) and with predictive model of pathologic stage. | baseline and then at 2-3 months | 
| Gene expression changes | To validate DCFPyL PET-MRI fusion or PET/MRI uptake in prostate cancer (quantified as per sextant SUVmax, SUVavg, metabolic tumor volume, total lesion DCFPyL uptake, DCFPyL uptake rate) as a reliable non-invasive imaging biomarker of AR signaling following ADT as determined by AR gene set expression of biopsy core tissue specimens using qPCR. | Baseline and then at 2-3 months | 
| Nodal metastatic disease changes | To compare the detection of nodal metastatic disease by DCFPyL PET-MRI fusion or PET/MRI at initial staging to detection by available conventional imaging modalities (bone scan, CT, MRI) and when available biopsy pathology. | Baseline and then at 2-3 months | 
| All cause DCFPyL PET-MRI fusion or PET/MRI toxicity | To determine the safety of DCFPyL. | Baseline and then at 2-3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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radiotracer