Androgen Receptor Signaling and Prostate-Specific Membrane Antigen Expression

Early Phase 1

Recruiting

• Conditions: Prostate Adenocarcinoma; Metastatic Hormone-Sensitive Prostate Cancer (mHSPC); Prostate Cancer
• Interventions: Drug: Apalutamide [Erleada], darolutamide [Nubeqa], or enzalutamide [Xtandi]; Diagnostic Test: Prostate-Specific Membrane Antigen (PSMA) PET/CT Scan

• Registration Number: NCT05683964
• Lead Sponsor: Beth Israel Deaconess Medical Center

Brief Summary

The goal of this research study is to determine whether hormonal therapies used early in the course of prostate cancer could increase the amount of Prostate-Specific Membrane Antigen (PSMA) as detected by PET/CT scans for participants with recurrent prostate cancer. This study will measure PSMA levels using standard PET/CT scans and participants will receive standard-of-care androgen receptor antagonist monotherapy.

The names of the treatment interventions involved in this study are:

* Androgen receptor antagonist monotherapy.

* PSMA PET/CT scan

It is expected that about 15 people will take part in this research study.

Participation in this research study is expected to last about 4 weeks.

Detailed Description

This research study is a pilot study, and it is the first time investigators are directly examining the effect of standard androgen receptor antagonists on Prostate-Specific Membrane Antigen (PSMA) expression for participants with recurrent, asymptomatic, metastatic hormone-sensitive prostate cancer (mHSPC). This study will measure PSMA levels using standard PET/CT scans and participants will receive standard-of-care androgen receptor antagonist monotherapy.

The research study procedures include screening for eligibility, study imaging and evaluations, blood collections, and follow up visits.

The names of the treatment interventions involved in this study are:

* Androgen receptor antagonist monotherapy.

* PSMA PET/CT scan

The U.S. Food and Drug Administration (FDA) has approved apalutamide, darolutamide, and enzalutamide for the treatment of prostate cancer.

It is expected that about 15 people will take part in this research study.

Participation in this research study is expected to last about 4 weeks.

Funding for this research study is provided by a philanthropic gift.

Study Timeline

• Study First Submitted: 2022-12-19
• Study First Submitted QC: 2023-01-04
• Study First Posted: 2023-01-13
• Study Start: 2023-01-19
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-15
• Last Update Posted: 2024-08-16
• Primary Completion: 2025-09-01
• Study Completion: 2026-02-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 15

Inclusion Criteria

• Patients age 40 or higher with prostate cancer that has been previously treated with primary definitive local therapies (prostatectomy with or without salvage radiation, or primary prostate radiation) and subsequently experiencing rising PSA meeting criteria for biochemical failure (PSA >0.2 ng/dL x2 following prostatectomy, or PSA > 2 + nadir value following primary radiation).
• PSMA PET/CT (Ga68, piflutolastat F-18, or other FDA-approved tracer) during time of biochemical recurrence, and within 6 weeks of registration, showing at least one lesion suspicious for recurrent prostate cancer based on size and/or SUV.
• Testosterone >100 ng/dL within 6 months prior to enrollment with no intervening hormonal therapies.
• Assigned by treating physician to receive standard-of-care AR antagonist monotherapy, using FDA-approved apalutamide, darolutamide, or enzalutamide.

Exclusion Criteria

• High disease burden, significant symptoms of disease, or other clinical situation requiring medical/surgical castration and/or docetaxel during the time of the study.
• Not suitable for AR antagonist therapy (e.g. inability to swallow pills, poor adherence, advanced liver disease, prohibitive co-payment without available patient assistance funding, contraindicated drug-drug interaction).
• Older-generation AR antagonists (e.g. bicalutamide) are not allowed on study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Androgen Receptor Antagonist Monotherapy	Apalutamide [Erleada], darolutamide [Nubeqa], or enzalutamide [Xtandi]	* Participants will receive pre-determined doses of apalutamide, darolutamide, or enzalutamide per standard care. * Participants will undergo Prostate-Specific Membrane Antigen (PSMA) PET/CT scans at weeks 1 and 4.
Androgen Receptor Antagonist Monotherapy	Prostate-Specific Membrane Antigen (PSMA) PET/CT Scan	* Participants will receive pre-determined doses of apalutamide, darolutamide, or enzalutamide per standard care. * Participants will undergo Prostate-Specific Membrane Antigen (PSMA) PET/CT scans at weeks 1 and 4.

Primary Outcome Measures

Name	Time	Method
Proportion of Participants with New Lesions (Flare)	week 4	Defined as the percentage of patients having the appearance of at least one new suspicious lesion or increase in SUV max relative to each individual's baseline.

Secondary Outcome Measures

Name	Time	Method
Changes in serum PSA	week 4
Changes in tumor size	week 4	Defined as maximum diameter of lesions for up to 5 target lesions. Standardized Uptake Value Max and Mean.
Changes in tumor SUV	week 4	For up to 5 target lesions. Standardized Uptake Value Max and Mean.

Trial Locations

Locations (1)

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States