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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Castration Resistant Prostate Cancer, Castration Sensitive Prostate Cancer, Prostate Adenocarcinoma

Intervention / Treatment
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* Drug: Piflufolastat
* Procedure: PSMA PET/CT Scan
* Procedure: PSMA PET/MRI scan
* Procedure: Biospecimen Collection
* Other: Electronic Health Record Review


Participation Criteria
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Eligibility Criteria
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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 histologically confirmed prostate adenocarcinoma. 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 four weeks of the initial PSMA PET. 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 (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.

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: CRPC<br>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. | Drug: Piflufolastat<br>* Given IV<br>* Other names: Fluorine F 18 DCFPyL;Procedure: PSMA PET/CT Scan<br>* Undergo PSMA PET/CT<br>* Other names: PSMA-Positron emission tomography/CT;Procedure: PSMA PET/MRI scan<br>* Undergo PET/MRI<br>* Other names: PSMA-Positron emission tomography/magnetic resonance imaging;Procedure: Biospecimen Collection<br>* Undergo collection of blood samples<br>* Other names: Lab draw;Other: Electronic Health Record Review<br>* Ancillary studies<br>|
| Experimental: Cohort 2: CSPC<br>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. | Drug: Piflufolastat<br>* Given IV<br>* Other names: Fluorine F 18 DCFPyL;Procedure: PSMA PET/CT Scan<br>* Undergo PSMA PET/CT<br>* Other names: PSMA-Positron emission tomography/CT;Procedure: PSMA PET/MRI scan<br>* Undergo PET/MRI<br>* Other names: PSMA-Positron emission tomography/magnetic resonance imaging;Procedure: Biospecimen Collection<br>* Undergo collection of blood samples<br>* Other names: Lab draw;Other: Electronic Health Record Review<br>* Ancillary studies<br>|

What is the study measuring?
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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. | 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. | 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 |  | Baseline PSMA PET up to 28 days after therapy initiation |