Evaluation of the Change in PSMA Expression in Prostate Cancer in Response to Hormonal Therapy

October 23, 2025 updated by: Nadine Mallak, MD, OHSU Knight Cancer Institute

Modulation of PSMA Expression in Castration Sensitive and Castration Resistant Prostate Cancer in Response to Hormonal Therapy

This clinical trial investigates the change in prostate-specific membrane antigen (PSMA) expression in response to hormonal therapy in both, Castration Sensitive Prostate Cancer (CSPC) and Castration Resistant Prostate Cancer (CRPC), and whether this change in PSMA expression changes tumor staging after therapy initiation. Understanding these effects can help define the best timing to perform the PSMA positron emission tomography (PET) relative to the start of therapy.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVE:

I. To determine the early effects (at day 8) of hormonal therapy on PSMA modulation in patients with castration sensitive prostate cancer (CSPC) and castration resistant prostate cancer (CRPC)

SECONDARY OBJECTIVES:

I. To evaluate the effects of hormonal therapy on PSMA modulation at day 28 post-therapy in patients with CSPC and CRPC

II. To evaluate whether the change in PSMA modulation after hormonal therapy initiation changes the tumor staging on PSMA PET as defined by the PROMISE V2 criteria.

EXPLORATORY OBJECTIVES:

I. To assess whether the initial change in PSMA modulation in response to hormonal therapy holds prognostic implications

II. To assess for potential correlation between the early change in PSMA modulation and tumor characteristics such as Gleason score, and site of disease.

III. To assess whether the baseline level of PSMA uptake holds prognostic implications in response to hormonal therapy

OUTLINE:

Patients will be divided (non-randomized) into 2 groups (CRPC or CSPC) and receive PSMA PET prior to start of therapy (standard of care), then again 8 days and 28 days after initiation of hormonal therapy.

Participants will be followed for up to 5 years.

Study Type

Interventional

Enrollment (Estimated)

80

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Oregon
      • Portland, Oregon, United States, 97239
        • Recruiting
        • OHSU Knight Cancer Institute
        • Contact:
        • Principal Investigator:
          • Nadine Mallak, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Participant or legally authorized representative (LAR) must provide written informed consent before any study-specific procedures or interventions are performed.
  • Participants must have confirmed prostate adenocarcinoma, histologically, or by combined imaging and biochemical markers.
  • Age >= 18 years. Given the nature of the disease in question, only men will be included. Members of all races and ethnic groups will be included.
  • Participants must have sites of prostate cancer showing uptake on an initial PSMA PET scan.

  • Participants are planned to receive hormonal therapy within eight weeks of the initial PSMA PET. The hormonal therapy agents include:

    • For CSPC: GnRH agonists, GnRH antagonists, first-generation antiandrogen (e.g. bicalutamide), or androgen receptor (AR)-targeted agent (e.g. Abiraterone, Enzalutamide, Apalutamide, Darolutamide)
    • For CRPC: this group of patients are typically on continuous ADT (GnRH agonists or antagonists), which will be continued, and the hormonal therapy they will be started on is an androgen receptor (AR)-targeted agent (e.g. Abiraterone, Enzalutamide, Apalutamide, Darolutamide)
  • Life expectancy > 3 months.
  • Cohort 1: Castration resistant prostate cancer with rising PSA (confirmed by two PSA values at least 1 week apart), testosterone < 50 ng/dL, on continuous ADT at least 4 months, no AR targeted agent in the prior 4 months.
  • Cohort 2: Castration sensitive prostate cancer with no ADT or AR targeted agents use in the past 12 months, testosterone >50 ng/dL

Exclusion Criteria:

  • Uncontrolled serious infection.
  • Intercurrent illness or condition that would limit compliance with study requirements.
  • Participants who have undergone any cancer treatment other than the hormonal therapy (systemic or radiation therapy) or who have started any supplements or herbal medications intended to treat cancer between the baseline PSMA PET and PSMA PET at day 28.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1: CRPC
Patients with CRPC will receive 18F-DCFPyL PET prior to start of therapy (standard of care), then again 8 days and 28 days after initiation of hormonal therapy.
Procedure: Biospecimen Collection
Undergo collection of blood samples
Other Names:
  • Biological Sample Collection
  • Specimen Collection
  • Lab draw
Other: Electronic Health Record Review
Ancillary studies
Drug: Piflufolastat
Given IV
Other Names:
  • 18F-DCFPyL
  • Fluorine F 18 DCFPyL
  • Piflufolastat F-18
  • Pylarify
Procedure: PSMA PET/CT Scan
Undergo PSMA PET/CT
Other Names:
  • PSMA PET/CT
  • Prostate-Specific Membrane Antigen PET/CT
  • PSMA-Positron emission tomography/CT
Procedure: PSMA PET/MRI scan
Undergo PET/MRI
Other Names:
  • Prostate-Specific Membrane Antigen PET/MRI
  • PSMA PET/MR
  • PSMA-Positron emission tomography/magnetic resonance imaging
Experimental: Cohort 2: CSPC
Patients with CSPC will receive 18F-DCFPyL PET prior to start of therapy (standard of care), then again 8 days and 28 days after initiation of hormonal therapy.
Procedure: Biospecimen Collection
Undergo collection of blood samples
Other Names:
  • Biological Sample Collection
  • Specimen Collection
  • Lab draw
Other: Electronic Health Record Review
Ancillary studies
Drug: Piflufolastat
Given IV
Other Names:
  • 18F-DCFPyL
  • Fluorine F 18 DCFPyL
  • Piflufolastat F-18
  • Pylarify
Procedure: PSMA PET/CT Scan
Undergo PSMA PET/CT
Other Names:
  • PSMA PET/CT
  • Prostate-Specific Membrane Antigen PET/CT
  • PSMA-Positron emission tomography/CT
Procedure: PSMA PET/MRI scan
Undergo PET/MRI
Other Names:
  • Prostate-Specific Membrane Antigen PET/MRI
  • PSMA PET/MR
  • PSMA-Positron emission tomography/magnetic resonance imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in maximum standardized uptake value (SUVmax) on post-therapy initiation PSMA PET (8 ± 2 days) compared to baseline.
Time Frame: Baseline PSMA PET up to 8 days after therapy initiation
Evaluate the change in SUVmax between baseline and Day 8 using a paired t-test to determine how hormonal therapy affects the PSMA modulation.
Baseline PSMA PET up to 8 days after therapy initiation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in SUVmax on post-therapy initiation PSMA PET (28 ± 3 days) compared to baseline.
Time Frame: Baseline PSMA PET up to 28 days after therapy initiation
Evaluate the change in SUVmax between baseline and Day 28 using a paired t-test to determine how hormonal therapy affects the PSMA modulation.
Baseline PSMA PET up to 28 days after therapy initiation
Number of patients in whom the tumor staging changed on PSMA PET scans obtained post-therapy initiation relative to baseline PET scan
Time Frame: Baseline PSMA PET up to 28 days after therapy initiation
Baseline PSMA PET up to 28 days after therapy initiation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

OHSU Knight Cancer Institute

Collaborators

Oregon Health and Science University
Progenics Pharmaceuticals, Inc.

Investigators

  • Principal Investigator: Nadine Mallak, MD, OHSU Knight Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 25, 2024

Primary Completion (Estimated)

September 1, 2028

Study Completion (Estimated)

September 1, 2030

Study Registration Dates

First Submitted

June 16, 2023

First Submitted That Met QC Criteria

June 16, 2023

First Posted (Actual)

June 26, 2023

Study Record Updates

Last Update Posted (Estimated)

October 24, 2025

Last Update Submitted That Met QC Criteria

October 23, 2025

Last Verified

October 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY00025799
  • NCI-2023-06184 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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