Androgen Deprivation Therapy (Relugolix) for the Improvement of Diagnostic Imaging (PSMA PET/CT Scan) in Patients With High Risk or Very High Risk Prostate Cancer, The EnrichPSMA Trial

NCT07025369 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: MC240503NCI-2025-0396525-002008
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well a short course of androgen deprivation therapy (ADT) with relugolix works in increasing expression of prostate-specific membrane antigen (PSMA) and improving diagnostic imaging with PSMA positron emission tomography (PET)/computed tomography (CT) in patients with high risk or very high risk prostate cancer. PSMA PET/CT has become the standard of care in imaging for high-risk prostate cancer. However, a limitation of PSMA PET/CT is its ability to detect cancer that has spread to the lymph nodes. PSMA is a protein that is usually found on the surface of normal prostate cells but is found in higher amounts on prostate tumor cells. Studies have shown that expression of PSMA is regulated by androgens (male reproductive hormones). Relugolix binds to gonadotropin-releasing hormone receptors in the pituitary gland, which blocks the pituitary gland from making the hormones follicle-stimulating hormone and luteinizing hormone. This causes the testicles to stop making testosterone. Relugolix may stop the growth of tumor cells that need testosterone to grow. PSMA PET/CT is an imaging procedure that is used to help find prostate tumor cells in the body. For this procedure, a cell-targeting molecule linked to a radioactive substance (flotufolastat F 18 in this trial) is injected into the body and travels through the blood. It attaches to PSMA that is found on the surface of prostate tumor cells. PET/CT scanners detect high concentrations of the radioactive molecule and shows where the prostate tumor cells are in the body. Giving a short course of ADT with relugolix may increase PSMA expression to detect smaller areas of prostate cancer that were not previously detected.

Conditions

Prostate Adenocarcinoma; Stage IIC Prostate Cancer AJCC v8; Stage III Prostate Cancer AJCC v8; Stage IV Prostate Cancer AJCC v8

Outcome Measures

Primary Outcomes (2)

• Maximum standard uptake value (SUVmax) for pre and post androgen deprivation therapy (ADT) prostate-specific antigen (PSMA) positron emission tomography (PET)

  Will be compared in all patients (pooled across randomization groups). We will explore differences between 5, 10 and 15 days since ADT initiation as hypothesis-generating, but the study will not be powered to detect differences between these groups.

  Day 0 up to day 15

• Mean standard uptake value (SUVmean) for pre and post ADT PSMA PET

  Will be compared in all patients (pooled across randomization groups). We will explore differences between 5, 10 and 15 days since ADT initiation as hypothesis-generating, but the study will not be powered to detect differences between these groups

  Day 0 up to day 15

Secondary Outcomes (3)

• Lymph node sensitivity of the pre and post ADT PSMA PET with surgical pathology as standard of truth

  Day 0 up to day 15

• Lymph node PSMA avidity between pre and post ADT PSMA using flotufolastat F 18 PET/computed tomography (CT)

  Day 0 up to day 15

• Incidence of adverse events (AEs)

  Up to 90 days of 2nd PSMA PET/CT

Study Arms (3)

Arm A (5 days of relugolix, flotufolastat F 18 PET/CT)

EXPERIMENTAL

Patients receive flotufolastat F 18 and undergo PET/CT on day 0. Patients then receive relugolix PO QD on days 1-5 in the absence of disease progression or unacceptable toxicity. Patients also receive flotufolastat F 18 and undergo PET/CT on day 5. Patients then undergo robotic radical prostatectomy with pelvic lymph node dissection within 90 days of 2nd flotufolastat F 18 PET/CT scan. In addition, patients undergo collection of blood samples throughout the study.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Other: Flotufolastat F-18 Gallium; Procedure: Laparoscopic Radical Prostatectomy with Robotics; Procedure: Pelvic Lymphadenectomy; Procedure: Positron Emission Tomography; Drug: Relugolix

Arm B (10 days of relugolix, flotufolastat F 18, PET/CT)

EXPERIMENTAL

Patients receive flotufolastat F 18 and undergo PET/CT on day 0. Patients then receive relugolix PO QD on days 1-10 in the absence of disease progression or unacceptable toxicity. Patients also receive flotufolastat F 18 and undergo PET/CT on day 10. Patients then undergo robotic radical prostatectomy with pelvic lymph node dissection within 90 days of 2nd flotufolastat F 18 PET/CT scan. In addition, patients undergo collection of blood samples throughout the study.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Other: Flotufolastat F-18 Gallium; Procedure: Laparoscopic Radical Prostatectomy with Robotics; Procedure: Pelvic Lymphadenectomy; Procedure: Positron Emission Tomography; Drug: Relugolix

Arm C (15 days of relugolix, flotufolastat, F 18 PET/CT)

EXPERIMENTAL

Patients receive flotufolastat F 18 and undergo PET/CT on day 0. Patients then receive relugolix PO QD on days 1-15 in the absence of disease progression or unacceptable toxicity. Patients also receive flotufolastat F 18 and undergo PET/CT on day 15. Patients then undergo robotic radical prostatectomy with pelvic lymph node dissection within 90 days of 2nd flotufolastat F 18 PET/CT scan. In addition, patients undergo collection of blood samples throughout the study.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Other: Flotufolastat F-18 Gallium; Procedure: Laparoscopic Radical Prostatectomy with Robotics; Procedure: Pelvic Lymphadenectomy; Procedure: Positron Emission Tomography; Drug: Relugolix

Interventions

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm A (5 days of relugolix, flotufolastat F 18 PET/CT); Arm B (10 days of relugolix, flotufolastat F 18, PET/CT); Arm C (15 days of relugolix, flotufolastat, F 18 PET/CT)

Computed Tomography PROCEDURE

Undergo PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Arm A (5 days of relugolix, flotufolastat F 18 PET/CT); Arm B (10 days of relugolix, flotufolastat F 18, PET/CT); Arm C (15 days of relugolix, flotufolastat, F 18 PET/CT)

Flotufolastat F-18 Gallium OTHER

Given flotufolastat F 18

Also known as: (18F)-rhPSMA-7.3, 18F-rhPSMA-7.3, 18FrhPSMA-7.3, F-18-rhPSMA-7.3, Fluorine F 18 Radiohybrid PSMA-7.3, Fluorine F 18 rhPSMA-7.3, Fluorine-18 rhPSMA-7.3, Posluma, rhPSMA-7.3 (18F)

Arm A (5 days of relugolix, flotufolastat F 18 PET/CT); Arm B (10 days of relugolix, flotufolastat F 18, PET/CT); Arm C (15 days of relugolix, flotufolastat, F 18 PET/CT)

Laparoscopic Radical Prostatectomy with Robotics PROCEDURE

Undergo robotic assisted radical prostatectomy

Also known as: RARP, Robot-assisted Radical Prostatectomy

Arm A (5 days of relugolix, flotufolastat F 18 PET/CT); Arm B (10 days of relugolix, flotufolastat F 18, PET/CT); Arm C (15 days of relugolix, flotufolastat, F 18 PET/CT)

Pelvic Lymphadenectomy PROCEDURE

Undergo pelvic lymph node dissection

Also known as: Excision Pelvic Lymph Nodes, Pelvic Lymph Node Dissection

Arm A (5 days of relugolix, flotufolastat F 18 PET/CT); Arm B (10 days of relugolix, flotufolastat F 18, PET/CT); Arm C (15 days of relugolix, flotufolastat, F 18 PET/CT)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Arm A (5 days of relugolix, flotufolastat F 18 PET/CT); Arm B (10 days of relugolix, flotufolastat F 18, PET/CT); Arm C (15 days of relugolix, flotufolastat, F 18 PET/CT)

Relugolix DRUG

Given PO

Also known as: N-(4-(1-((2,6-Difluorophenyl)methyl)-5-((dimethylamino)methyl)-1,2,3,4-tetrahydro-3-(6-methoxy-3-pyridazinyl)-2,4-dioxothieno(2,3-d)pyrimidin-6-yl)phenyl)-N'-methoxyurea, Orgovyx, Relumina, TAK 385, TAK-385, TAK385

Arm A (5 days of relugolix, flotufolastat F 18 PET/CT); Arm B (10 days of relugolix, flotufolastat F 18, PET/CT); Arm C (15 days of relugolix, flotufolastat, F 18 PET/CT)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Histological confirmation of prostate adenocarcinoma
• Diagnosis of high risk or very high risk prostate cancer per National Comprehensive Cancer Network (NCCN) Risk Stratification. \[Any of the following: grade group 4 or 5, prostate-specific antigen (PSA) greater than 20, radiographic cT3 on MRI\]
• Testosterone greater than or equal to 300
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
• Hemoglobin ≥ 9.0 g/dL (obtained ≤ 120 days prior to registration/randomization)
• Absolute neutrophil count (ANC) ≥ 1500/mm\^3 (obtained ≤ 120 days prior to registration/randomization)
• Platelet count ≥ 100,000/mm\^3 (obtained ≤ 120 days prior to registration/randomization)
• Male patients who are committed to undertaking the following measures for the duration of the study and after the last dose of ORGOVYX (relugolix) for the time period specified:
• Use a condom during sex while being treated and for 30 days after the last dose of ORGOVYX (relugolix)
• Do not make semen donations during treatment and for 30 days after the last dose of ORGOVYX (relugolix)
• Those with female partners of childbearing potential may be enrolled if they are:
• Documented to be surgically sterile (i.e., vasectomy);
• Committed to practicing true abstinence during treatment and for 30 days after the last ORGOVYX (relugolix) dose; or
• Committed to using an effective method of contraception with their partner during treatment and for 30 days following the last dose of ORGOVYX (relugolix)

You may not qualify if:

• Any of the following prior therapies:
• Chemotherapy ≤ 2 weeks prior to registration/randomization
• Androgen deprivation therapy
• Pelvic radiation
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• Uncontrolled intercurrent illness including, but not limited to:
• Ongoing or active infection
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Or psychiatric illness/social situations that would limit compliance with study requirements
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
• Other active malignancy ≤ 1 year prior to registration
• EXCEPTIONS: Non-melanotic skin cancer
• NOTE: If there is a history of prior malignancy, they must not be receiving other active treatment for their cancer

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

RECRUITING

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Specimen Handling; Robotics; Magnetic Resonance Spectroscopy; relugolix

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Automation; Technology; Technology, Industry, and Agriculture; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Jack R. Andrews, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trials Referral Office

CONTACT

855-776-0015; mayocliniccancerstudies@mayo.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2025
• First Posted: June 17, 2025
• Study Start: August 25, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 13, 2026

Record last verified: 2026-03

Locations

US (1)