PSMA-based 18F-DCFPyL PET/CT and PET/MRI Pilot Studies in Prostate Cancer

Study Overview
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Brief Summary
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The overall goal of this research is to validate and develop a non-invasive imaging biomarker of prostate cancer detection, progression, and recurrence. Development of such a biomarker may be useful to differentiate indolent from aggressive prostate cancer phenotypes allowing for selection of an appropriate risk adaptive therapy.

Detailed Description
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The investigators propose to evaluate a novel second-generation low-molecular-weight prostate specific membrane antigen (PSMA)-based positron emission tomography (PET) agent, 18F-DCFPyL, for detection of primary and metastatic prostate cancer. 18F-DCFPyL PET demonstrates very high tumor-to-background and tumor specific uptake which may allow for a more sensitive and accurate method for detection of early tumor recurrence and metastatic disease as compared to current PET radiotracers and current standard-of-care imaging including 99mTc-methylene diphosphonate bone scintigraphy (bone scan), contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI). Primary Objectives: The investigators propose to evaluate this PET agent for four different prostate cancer clinical scenarios. detection of clinically significant high-grade prostate cancer and initial staging detection of sites of recurrence in the setting of biochemical recurrence after definitive prostatectomy detection of advanced androgen-resistant metastatic prostate cancer, and detection of clinically significant prostate cancer in very low to intermediate risk primary prostate cancer Secondary Objectives: Evaluate the performance of 18F-DCFPyL PET and MRI whole body DWI for detection of local-nodal and distant metastatic disease on initial staging compared to conventional imaging modalities (CT and bone scintigraphy). Correlate 18F-DCFPyL PET standardized-uptake values (SUV) and MRI parameters with PSMA expression by prostatectomy pathology IHC. Evaluate the specificity of 18F-DCFPyL PET for differentiating primary prostate cancer versus non-malignant prostate lesions (BPH, prostatitis). Comparison of whole body low-dose CT and whole body MRI derived PET SUV-quantitation. Evaluate the performance of dedicated pelvic 18F-DCFPyL PET/MRI with dynamic PET acquisition and multi-parametric MRI for differentiation of urine versus recurrent malignancy in the prostatectomy bed. Evaluate the contribution of whole body MRI DWI obtained from PET/MRI to improve the diagnostic performance of 18F-DCFPyL PET/CT and PET/MRI for metastatic prostate cancer lesion detection. Assess the quantitative accuracy of PET-derived standardized uptake value (SUV)-based parameters in 18F-DCFPyL PET obtained from PET/MRI versus PET/CT. Assess the quantitative reproducibility of 18F-DCFPyL PET/CT derived-SUV values in normal organ and metastatic tumor lesions. Evaluate the ability of 18F-DCFPyL PET to improve detection of clinically significant primary prostate cancer in men with very low to intermediate risk prostate cancer under active surveillance or watchful waiting. Update: As of July 2022 verification, the investigators are no longer enrolling into sub-studies 1 and 2.

Official Title
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PSMA-based 18F-DCFPyL PET/CT and PET/MRI Pilot Studies in Prostate Cancer

Conditions
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Prostate Cancer, Prostate Neoplasm

Intervention / Treatment
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* Drug: 18F-DCFPyL PET


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Prostate cancer pathologically proven by prostate biopsy (newly diagnosed for Sub-Study 1 and 4) Prostate biopsy histology grade ≥ Gleason 1, 6, 3+4, or 4+3; positive biopsy >2 cores Any PSA permitted Two consecutive rising PSA values (Sub-Study 3 only) Castrate-levels of testosterone - total testosterone < 50 ng/dL (Sub-Study 3 only) Patients considered as candidates for and medically fit to undergo prostatectomy At least 7 days after most recent prostate biopsy Imaging evidence of suspected metastatic disease, including CT, bone scan, MRI, ultrasound or other PET modalities (Sub-Study 3 only) New diagnosis of prostate cancer undergoing additional biopsy evaluation (Sub--Study 4 only) Karnofsky performance status of at least 70 (Sub-Study 4 only) General health and anatomy suitable to undergo transrectal ultrasound-MRI fusion biopsy of the identified lesions and standard 12 core sextent biopsy (Sub-Study 4 only) Exclusion Criteria: Prior pelvic external beam radiation therapy or brachytherapy Chemotherapy for prostate cancer Androgen deprivation therapy for prostate cancer Investigational therapy for prostate cancer (Sub-Study 3 Only) Unable to lie flat during or tolerate PET/CT Prior history of any other malignancy within the last 2 years, other than skin basal cell or cutaneous superficial squamous cell carcinoma that has not metastasized and superficial bladder cancer. No prostatectomy scheduled more than 12 hours post imaging (Sub-Study 1 only) Serum creatinine > 2 time the upper limit of normal Total bilirubin > 3 times the upper limit of normal Liver Transaminases > 5 times the upper limit of normal

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: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: Single center, open label, single-arm, pilot study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 18F-DCFPyL PET<br>Four separate substudies evaluating 18F-DCFPyL PET imaging of prostate cancer in four prostate cancer clinical scenarios under the following subheadings: (1) primary prostate cancer, (2) biochemical recurrence post-prostatectomy prior to radiation therapy, (3) androgen-resistant metastatic disease and (4) detection of clinically significant prostate cancer in low to intermediate risk primary prostate cancer | Drug: 18F-DCFPyL PET<br>* 18F-DCFPyL PET demonstrates very high tumor-to-background and tumor specific uptake which may allow for a more sensitive and accurate method for detection of early tumor recurrence and metastatic disease as compared to current PET radiotracers and current standard-of-care imaging including 99mTc-methylene diphosphonate bone scintigraphy (bone scan), contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 18F-DCFPyL PSMA-based PET and multi-parametric MRI with DWI for Sub-Study 1: Primary Prostate Cancer | To evaluate the performance of 18F-DCFPyL PSMA-based PET and multi-parametric MRI (MP-MRI) with DWI (Diffusion Weighted Imaging) and gadolinium DCE (Dynamic Contrast Enhanced) using a dedicated PET/MRI scanner to detect clinically significant larger volume high-grade primary prostate cancer based on prostatectomy step-section pathology correlation. | one study visit (up to 3.5 hours) | 
| Evaluate 18F-DCFPyL PSMA-based PET for localization for Sub-Study 2: Biochemical Recurrence | To evaluate the performance of 18F-DCFPyL PSMA-based PET for localization of the site of recurrent prostate cancer in men with biochemical recurrence after definitive prostatectomy with planned salvage external-beam radiation therapy (EBRT). PSA response to prostatic fossa salvage irradiation will be compared with pre-salvage 18F-DCFPyL PET uptake in the radiation field. | one study visit (up to 3.5 hours) | 
| Compare detectability of 18F-DCFPyL for Sub-Study 3: Metastatic Androgen-Resistant Prostate Cancer | To compare the detectability of metastatic prostate cancer using 18F-DCFPyL PET obtained from PET/CT and PET/MRI compared to conventional imaging modalities (CIM) (bone scan and CT) in men with androgen-resistant prostate cancer. | up to 7 days | 
| Sub-Study 4: Rate of positive cancer detection using PET/MRI directed MRI/transrectal ultrasound (TRUS) fusion biopsy with and without additional PSMA PET information | To evaluate the ability of 18F-DCFPyL PSMA PET to improve detection of clinically significant cancer in men with very low to intermediate risk prostate cancer using a dedicated PET/MRI. | one study visit (up to 3.5 hours) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sub-study 1: Detection of local-nodal and distant metastatic disease (PET | Evaluate the performance of 18F-DCFPyL PET and MRI whole body DWI for detection of local-nodal and distant metastatic disease on initial staging compared to conventional imaging modalities (CT and bone scintigraphy). | one study visit (up to 3.5 hours) | 
| Sub-Study 1: Correlation of 18F-DCFPyL PET and MRI | Correlate 18F-DCFPyL PET standardized-uptake values (SUV) and MRI parameters with PSMA expression by prostatectomy pathology IHC. | one study visit (up to 3.5 hours) | 
| Sub-Study 1: Specificity of 18F-DCFPyL | Evaluate the specificity of 18F-DCFPyL PET for differentiating primary prostate cancer versus non-malignant prostate lesions (BPH, prostatitis). | one study visit (up to 3.5 hours) | 
| Sub-Study 1: Low-dose CT versus MRI derived PET SUV | Comparison of whole body low-dose CT and whole body MRI derived PET SUV-quantitation. | one study visit (up to 3.5 hours) | 
| Sub-Study 2: Detection of local-nodal and distant metastatic disease (pelvic) | Comparison of whole body 18F-DCFPyL PET with pelvic MR-MRI and whole body DWI for detection of local-nodal and distant metastatic disease on initial staging compared to conventional imaging modalities (CT and bone scintigraphy). | one study visit (up to 3.5 hours) | 
| Sub-Study 2: Dedicated pelvic 18F-DCFPyL PET/MRI with dynamic PET acquisition and multi-parametric MRI | Evaluate the performance of dedicated pelvic 18F-DCFPyL PET/MRI with dynamic PET acquisition and multi-parametric MRI for differentiation of urine versus recurrent malignancy in the prostatectomy bed. | one study visit (up to 3.5 hours) | 
| Sub-Study 3: Contribution of whole body MRI DWI | Evaluate the contribution of whole body MRI DWI obtained from PET/MRI to improve the diagnostic performance of 18F-DCFPyL PET/CT and PET/MRI for metastatic prostate cancer lesion detection. | Up to 7 days | 
| Sub-Study 3: Quantitative accuracy | Assess the quantitative accuracy of 18F-DCFPyL PET standardized uptake value parameters from PET/MRI versus PET/CT. | Up to 7 days | 
| Sub-Study 3: Quantitative reproducibility | Assess the quantitative reproducibility of 18F-DCFPyL PET/CT derived-SUV values in normal organ and metastatic tumor lesions. | Up to 7 days | 
| Sub-study 4: Positive Detection Rate of Prostate Cancer via biopsy on PSMA PET versus mpMRI alone in very low to intermediate risk groups active surveillance and watchful waiting patients | Evaluate the positive detection rate of prostate cancer via biopsy on PSMA PET versus mpMRI alone in very low to intermediate risk groups active surveillance and watchful waiting patients. | one study visit (up to 3.5 hours) | 
| Sub-study 4: Detection rate of clinically significant prostate cancer in men with directed MRI/US biopsy | To evaluate the ability of PSMA PET alone versus mpMRI alone versus combined PSMA PET with mpMRI to detect clinically significant prostate cancer in men with directed MRI/US biopsy. | one study visit (up to 3.5 hours) | 
| Sub-study 4: Detection Rate of Prostate Cancer vs False Positive Findings via Biopsy | Evaluate the rate of detection of prostate cancer and false positive findings via biopsy and available prostatectomy histopathology on PSMA PET/MRI versus mpMRI alone in different prostate anatomic regions (transition, central, peripheral zones) in these risk cohorts. | one study visit (up to 3.5 hours) | 
| Sub-study 4: Number of Participants who change treatment and surgical management plans after inclusion of PSMA-based PET directed biopsy | Assess the change in treatment and surgical management plan before and after inclusion of PSMA-based PET directed biopsy histopathology information and additional pelvic and whole body PET/MRI PET information will be obtained. | one study visit (up to 3.5 hours) | 
| Sub-study 4: Correlation of PET and MRI parameters for PET and/or MRI positive lesions to biopsy histopathology, cancer grade group, PSA and other clinical parameters | Qualitative and quantitative PET and MRI parameters for PET and/or MRI positive lesions will be correlated with biopsy histopathology, cancer grade group, PSA and other clinical parameters. | one study visit (up to 3.5 hours) | 
| Sub-study 4: Change in Gleason Score | PET and MRI directed biopsy histopathology prostate Gleason score range will be compared, and evaluated for Gleason score upgrading in any patients who undergo prostatectomy with available prostatectomy histopathology as the reference standard. Gleason scores range from 6-10 with higher numbers indicating higher grade cancer. | one study visit (up to 3.5 hours), post-prostatectomy (standard of care) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate Cancer, Prostate neoplasm