Clinical trial NCT03232164: PSMA-based 18F-DCFPyL PET/CT and PET/MRI Pilot Studies in Prostate Cancer
Official title: PSMA-based 18F-DCFPyL PET/CT and PET/MRI Pilot Studies in Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Prostate Cancer
Prostate Neoplasm
Keywords: Prostate Cancer
Prostate neoplasm
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
First posted: 2017-07-27
Enrollment: 126
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single center, open label, single-arm, pilot study
Primary purpose: DIAGNOSTIC

Brief summary: 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: 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.

1. detection of clinically significant high-grade prostate cancer and initial staging
2. detection of sites of recurrence in the setting of biochemical recurrence after definitive prostatectomy
3. detection of advanced androgen-resistant metastatic prostate cancer, and
4. 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.

Eligibility criteria: 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

Primary outcomes:
measure: 18F-DCFPyL PSMA-based PET and multi-parametric MRI with DWI for Sub-Study 1: Primary Prostate Cancer
timeFrame: one study visit (up to 3.5 hours)
measure: Evaluate 18F-DCFPyL PSMA-based PET for localization for Sub-Study 2: Biochemical Recurrence
timeFrame: one study visit (up to 3.5 hours)
measure: Compare detectability of 18F-DCFPyL for Sub-Study 3: Metastatic Androgen-Resistant Prostate Cancer
timeFrame: up to 7 days
measure: 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
timeFrame: one study visit (up to 3.5 hours)
Secondary outcomes:
measure: Sub-study 1: Detection of local-nodal and distant metastatic disease (PET
timeFrame: one study visit (up to 3.5 hours)
measure: Sub-Study 1: Correlation of 18F-DCFPyL PET and MRI
timeFrame: one study visit (up to 3.5 hours)
measure: Sub-Study 1: Specificity of 18F-DCFPyL
timeFrame: one study visit (up to 3.5 hours)
measure: Sub-Study 1: Low-dose CT versus MRI derived PET SUV
timeFrame: one study visit (up to 3.5 hours)
measure: Sub-Study 2: Detection of local-nodal and distant metastatic disease (pelvic)
timeFrame: one study visit (up to 3.5 hours)
measure: Sub-Study 2: Dedicated pelvic 18F-DCFPyL PET/MRI with dynamic PET acquisition and multi-parametric MRI
timeFrame: one study visit (up to 3.5 hours)
measure: Sub-Study 3: Contribution of whole body MRI DWI
timeFrame: Up to 7 days
measure: Sub-Study 3: Quantitative accuracy
timeFrame: Up to 7 days
measure: Sub-Study 3: Quantitative reproducibility
timeFrame: Up to 7 days
measure: 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
timeFrame: one study visit (up to 3.5 hours)
measure: Sub-study 4: Detection rate of clinically significant prostate cancer in men with directed MRI/US biopsy
timeFrame: one study visit (up to 3.5 hours)
measure: Sub-study 4: Detection Rate of Prostate Cancer vs False Positive Findings via Biopsy
timeFrame: one study visit (up to 3.5 hours)
measure: Sub-study 4: Number of Participants who change treatment and surgical management plans after inclusion of PSMA-based PET directed biopsy
timeFrame: one study visit (up to 3.5 hours)
measure: 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
timeFrame: one study visit (up to 3.5 hours)
measure: Sub-study 4: Change in Gleason Score
timeFrame: one study visit (up to 3.5 hours), post-prostatectomy (standard of care)
Other outcomes:
Locations:
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Steve Y Cho, MD
role: PRINCIPAL_INVESTIGATOR
References: