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

Phase 4

Recruiting

• Conditions: Castration Resistant Prostate Cancer; Castration Sensitive Prostate Cancer; Prostate Adenocarcinoma
• Interventions: Drug: Piflufolastat; Procedure: PSMA PET/CT Scan; Procedure: PSMA PET/MRI scan; Procedure: Biospecimen Collection; Other: Electronic Health Record Review

• Registration Number: NCT05919329
• Lead Sponsor: OHSU Knight Cancer Institute

Brief Summary

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.

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 Timeline

• Study First Submitted: 2023-06-16
• Study First Submitted QC: 2023-06-16
• Study First Posted: 2023-06-26
• Study Start: 2024-06-25
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-09
• Last Update Posted: 2025-04-11
• Primary Completion: 2028-09-01
• Study Completion: 2030-09-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 80

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1: CRPC	Piflufolastat	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.
Cohort 1: CRPC	PSMA PET/CT Scan	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.
Cohort 1: CRPC	PSMA PET/MRI scan	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.
Cohort 1: CRPC	Biospecimen Collection	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.
Cohort 1: CRPC	Electronic Health Record Review	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.
Cohort 2: CSPC	Piflufolastat	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.
Cohort 2: CSPC	PSMA PET/CT Scan	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.
Cohort 2: CSPC	PSMA PET/MRI scan	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.
Cohort 2: CSPC	Biospecimen Collection	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.
Cohort 2: CSPC	Electronic Health Record Review	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.

Primary Outcome Measures

Name	Time	Method
Change in maximum standardized uptake value (SUVmax) on post-therapy initiation PSMA PET (8 ± 2 days) compared to baseline.	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.

Secondary Outcome Measures

Name	Time	Method
Change in SUVmax on post-therapy initiation PSMA PET (28 ± 3 days) compared to baseline.	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.
Number of patients in whom the tumor staging changed on PSMA PET scans obtained post-therapy initiation relative to baseline PET scan	Baseline PSMA PET up to 28 days after therapy initiation

Trial Locations

Locations (1)

OHSU Knight Cancer Institute; 🇺🇸 Portland, Oregon, United States