PSMA PET/MRI for Predicting and Detecting Prostate Cancer

PSMA PET/MRI to Predict Tumor Response to Neoadjuvant Systemic Therapy in Men With High-Risk Prostate Cancer, and Detection of Cancer in Men With Very Low to Intermediate-Risk Prostate Cancer

The goal of this clinical trial is to see if a drug called 18F-DCFPyL can help find prostate cancer or prostate cancer that has spread to other parts of the body. The main question it aims to answer is:

• Can 18F-DCFPyL predict response to therapy; and,
• Does 18F-DCFPyL improve detection of early signs of cancer.

Participants will undergo PET/MRI scans.

Study Overview

• Status: Not yet recruiting
• Conditions: Prostate Cancer; Intermediate Risk Prostate Cancer; Locally Advanced Prostate Cancer; Low-Risk Prostate Cancer; High-Risk Localized Prostate Cancer
• Intervention / Treatment: Device: PSMA PET; Device: MRI; Drug: 18F-DCFPyL

Detailed Description

Evaluate PSMA PET/MRI imaging as a method for determining:

1. Treatment response in primary prostate cancer after neoadjuvant systemic therapy in men with high-risk prostate cancer; and,
2. Detection of clinically significant cancer in men with very low to intermediate risk primary prostate cancer.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Abigail Wiedmer; Email: wiedmer@urology.wisc.edu
• Study Contact Backup: Name: Rad Study; Email: Radstudy@uwhealth.org

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53715
      • University of Wisconsin - Madison
      • Contact: Abigail Wiedmer; Email: wiedmer@urology.wisc.edu
      • Principal Investigator: Changhee Lee, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria - Sub-study 1:

• Participant must be ≥ 18 years of age

• Participant must have an ECOG performance status ≤ 1.

• High risk disease (NCCN criteria Gleason 8-10 or PSA>20) or oligometastatic

• Histologic confirmation of prostate adenocarcinoma of the prostate gland, with or without evidence of metastases (oligometastatic <10 sites) on imaging by conventional imaging (MRI, CT, or 99mTc bone scan) or PSMA PET/CT

• Newly diagnosed disease with no prior treatment (surgery, radiation or systemic treatment, hormone therapy or chemotherapy) to the primary disease

  • Participants may have started LHRH agonist or antagonist therapy, and/or androgen receptor signaling inhibitor (ARSI) as long as it was not started more than 30 days before the patient is enrolled on this study

• Participants will have i) enrolled on the METANOVA trial or ii) have selected androgen deprivation therapy prior to surgery as their treatment of choice

• Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria - Sub-study 1:

• Castration resistant prostate cancer (CRPC).

• Evidence of visceral or intracranial metastases.

• Participant receiving any other investigational agents for cancer.

• Participant is participating in a concurrent treatment protocol for cancer.

• Contraindications to MRI or intravenous contrast administration per institutional MRI safety screening including severe kidney disease, prior severe allergic reaction to gadolinium-based contrast, prior nephrogenic systemic fibrosis

• Unable to lie flat during or tolerate PET/MRI

• Prior definitive treatment to the primary prostate cancer or pelvis. Participants with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled diabetes (HgA1c > 10), active pituitary or adrenal dysfunction, or psychiatric illness/social situations that would limit compliance with study requirements

• History of another active malignancy within the previous 2 years, except for non-melanoma skin cancer, non-muscle invasive bladder cancer, or a malignancy that is considered cured with minimal risk of recurrence.

• Active Crohn's disease or ulcerative colitis despite medical management.

• Refusal to sign informed consent.

• Any condition that in the opinion of the investigator would preclude participation in this study.

• Participants requiring intravenous (IV) conscious sedation for imaging are not eligible; participants requiring mild, oral anxiolytics for the clinical MRI scan will be allowed to participate as long as the following criteria are met:

  1. The participant has their own prescription for the medication
  2. The informed consent process is conducted prior to the self-administration of the medication.
  3. The participant comes to the research visit with a driver or an alternative plan for transportation (e.g. Uber, taxi, etc.).

Inclusion Criteria - Sub-study 2:

• Male, 40-85 years of age

• New diagnosis of prostate cancer undergoing additional biopsy evaluation or high clinical suspicion of prostate cancer with elevated and rising PSA level.

• Participant with prostate cancer undergoing:

  • Reevaluation for progression on active surveillance or watchful waiting as manifest by rising PSA and/or change in digital-rectal exam OR
  • Participant on active surveillance or watchful waiting undergoing planned MRI/TRUS prostate biopsy for re-evaluation

• Meet criteria ranging from very low to intermediate risk group:

  • T1c to T2
  • Gleason-group (GG) 1 (Gleason score 6), GG2 (Gleason score 3+4) or GG3 (Gleason score 4+3) prostate adenocarcinoma
  • Any PSA permitted

• Karnofsky performance status of at least 70

• General health and anatomy suitable to undergo transrectal ultrasound-MRI fusion biopsy, as determined by SOC, of the identified lesions and standard 12 core sextent biopsy

• Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria - Sub-study 2:

• Prior pelvic external beam radiation therapy or brachytherapy

• Chemotherapy for prostate cancer

• Androgen deprivation therapy for prostate cancer

• Unable to lie flat during or tolerate PET/MRI

• 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.

• Contraindications to MRI or intravenous contrast administration per institutional MRI safety screening including severe kidney disease, prior severe allergic reaction to gadolinium-based contrast, prior nephrogenic systemic fibrosis.

• Participants requiring intravenous (IV) conscious sedation for imaging are not eligible; participants requiring mild, oral anxiolytics for the clinical MRI scan will be allowed to participate as long as the following criteria are met:

  1. The participant has their own prescription for the medication
  2. The informed consent process is conducted prior to the self-administration of the medication.
  3. The participant comes to the research visit with a driver or an alternative plan for transportation (e.g. Uber, taxi, etc.).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Men with high-risk prostate cancer (Study 1); Men with high-risk prostate cancer will undergo PSMA PET and MRI	Device: PSMA PET; Participants will complete 75 minutes of scans.; Device: MRI; Participants will complete 75 minutes of scans.; Drug: 18F-DCFPyL; 18F-DCFPyL will be injected through an IV in the arm.
Experimental: Men with very low to intermediate risk prostate cancer (Study 2); Men with very low to intermediate risk prostate cancer will undergo PSMA PET and MRI	Device: PSMA PET; Participants will complete 75 minutes of scans.; Device: MRI; Participants will complete 75 minutes of scans.; Drug: 18F-DCFPyL; 18F-DCFPyL will be injected through an IV in the arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic tumor volume (Study 1 only)	Imaging response between baseline and pre-prostatectomy PSMA PET/MRI will be measured to learn if it can predict final pathologic tumor volume. Evaluating whether changes in PSMA PET and MRI using quantitative imaging variables (SUV, tumor volume PSMA, ADC, DWI) from baseline to pre-prostatectomy imaging predict final pathologic tumor volume on whole-mount radical prostatectomy using 3D mold.	75 minutes
The ability of PSMA PET to improve detection of clinically significant cancer (Study 2)	The rate of positive cancer detection using PET/MRI directed MRI/transrectal ultrasound (TRUS) fusion biopsy with and without additional PSMA PET information	75 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Final pathologic tumor volume (Study 1)	Compare the ability of pre-prostatectomy PSMA PET/MRI versus mpMRI alone to predict final pathologic tumor volume.	75 minutes
Diagnostic accuracy (Study 2)	True positive, false positive rate of PSMA PET alone versus mpMRI alone versus combined PSMA PET with mpMRI on a lesion-based and patient-based analysis in patient with very low to intermediate risk prostate cancer	75 minutes
Rate of management change based on biopsy results (Study 2)	The rate of management change based on mpMRI-directed biopsy results alone versus mpMRI- and PSMA PET-directed biopsy results	Baseline, 18 months

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: Bluemke Family Trust
• Investigators: Principal Investigator: Changhee Lee, MD, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): December 1, 2031
• Study Completion (Estimated): December 1, 2031

Study Registration Dates

• First Submitted: October 27, 2026
• First Submitted That Met QC Criteria: November 6, 2026
• First Posted (Actual): November 9, 2026

Study Record Updates

• Last Update Posted (Actual): November 9, 2026
• Last Update Submitted That Met QC Criteria: November 6, 2026
• Last Verified: November 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; 2-(3-(1-carboxy-5-((6-fluoropyridine-3-carbonyl)amino)pentyl)ureido)pentanedioic acid
• Other Study ID Numbers: 2026-1501; UWMSN | SMPH | Radiology (Other Identifier: UW Madison); Protocol Version 10/2/2026 (Other Identifier: UW Madison)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No