An Investigational Scan (rhPSMA-7.3 PET/CT) for Detecting Biochemically Recurrent Prostate Cancer, ENLIGHTEN Trial

ENLIGHTEN: Detection by POSLUMA Following Negative Other PET-PSMA Imaging

This phase II trial evaluates an imaging technique (rhPSMA-7.3 positron emission tomography [PET]/computed tomography [CT]) for detecting prostate cancer in patients who have increasing prostate-specific antigen levels following prior treatment (biochemical recurrence) but who were prostate specific membrane antigen negative on their most recent PET scan. Contrast agents like rhPSMA-7.3 (also called POSLUMA) circulate in the blood until they find their intended target. Once they are taken up by the target tumor cells, they can be visualized using PET/CT cameras. A PET scan is a procedure in which a small amount of radioactive tracer (in this case rhPSMA-7.3) is injected into a vein, and a scanner is used to make detailed, computerized pictures of areas inside the body where the tracer is taken up. Because tumor cells often take up more tracer than normal cells, the pictures can be used to find tumor cells in the body. A CT scan is a procedure that uses a computer linked to an x-ray machine to make a series of detailed pictures of areas inside the body. The pictures are taken from different angles and are used to create 3-dimensional views of tissues and organs. Combining a PET scan with a CT scan can help make the image easier to interpret. PET/CT scans are hybrid scanners that combine both modalities into a single scan during the same examination. The researchers want to determine whether the rhPSMA7.3 PET/CT scan is useful for detecting biochemically recurrent prostate cancer in patients who were negative on prior non-POSLUMA PET imaging.

Study Overview

• Status: Recruiting
• Conditions: Biochemically Recurrent Prostate Carcinoma; Prostate Adenocarcinoma
• Intervention / Treatment: Procedure: Computed Tomography; Procedure: Positron Emission Tomography; Other: Electronic Health Record Review; Other: Flotufolastat F-18 Gallium

Detailed Description

PRIMARY OBJECTIVE:

I. Determine consensus detection rate by flotufolastat F-18 gallium (rhPSMA-7.3)-PET (POSLUMA) scan in men with recent negative non-POSLUMA PET prostate specific membrane antigen (PSMA) scans.

SECONDARY OBJECTIVES:

I. Determine patient level verified detection rates (by histopathology or a surrogate standard of truth [second contemporaneous imaging, treatment response/change in subsequent imaging]).

II. Determine change in management plan based on POSLUMA scan (major / minor).

EXPLORATORY OBJECTIVE:

I. Determine patient and patient disease characteristics consistent with a positive POSLUMA scan at prostate specific antigen (PSA) < 0.5ng/ml (i.e. pathological Gleason grade, PSA at scan, time to biochemical recurrence [BCR], prostate-specific antigen doubling time [PSADT]).

OUTLINE:

Patients receive rhPSMA-7.3 intravenously (IV) and undergo PET/CT 60 minutes later on day 1.

After completion of study intervention, patients are followed up at 14 days and then every 3 months for 2 years.

• Study Type: Interventional
• Enrollment (Estimated): 27
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Nikki Hubbard; Phone Number: 312-694-9001; Email: Nikki.Hubbard@northwestern.edu
• Study Contact Backup: Name: Sophia Kallas; Phone Number: 312-694-9001; Email: sophia.kallas@northwestern.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University
      • Contact: Ashley E. Ross; Phone Number: 312-694-9001; Email: Ashley.ross@nm.org
      • Principal Investigator: Ashley E. Ross

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men with a history of prostate adenocarcinoma treated with local therapy (including radical prostatectomy or radical prostatectomy and secondary therapy [i.e. salvage radiation])
• Men must have biochemical recurrence (defined as PSA >= 0.1ng/ml) after therapy
• PSA < 0.5ng/ml (within 90 days of enrollment)
• Men must have had negative or equivocal PET PSMA based imaging with 90 days of enrollment with an Food and Drug Administration (FDA) approved non-POSLUMA tracer
• Non-castrate testosterone (testosterone [T] > 50ng/dL) within 90 days of study entry
• Institutional Review Board (IRB)-/Independent Ethics Committee (IEC)-approved written informed consent and privacy language as per national regulations must be obtained from the subject or legally authorized representative prior to any study-related procedures
• Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on the study
• Concurrent diseases and malignancies are permitted

Exclusion Criteria:

• Most recent PSA not between 0.1ng/ml and 0.5ng/ml
• Men with non-metastatic castrate resistant prostate cancer (defined as rising PSA and T < 50ng/dl)
• Patients receiving 5-alpha reductase inhibitors, androgen deprivation therapy and androgen receptor antagonists within 3 months of enrollment (men may start these therapies at physician discretion immediately following POSLUMA PET PSMA scan)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Diagnostic (rhPSMA-7.3 PET/CT); Patients receive rhPSMA 7.3 IV and undergo PET/CT 60 minutes later on day 1.

Procedure: Computed Tomography; Undergo PET/CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Procedure: Positron Emission Tomography; Undergo PET/CT; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; PT; Positron emission tomography (procedure); Other: Electronic Health Record Review; Ancillary studies; Other: Flotufolastat F-18 Gallium; Given IV; Other Names: 18F-rhPSMA-7.3; rhPSMA-7.3 (18F); (18F)-rhPSMA-7.3; 18FrhPSMA-7.3; F-18-rhPSMA-7.3; Fluorine-18 rhPSMA-7.3; Fluorine F 18 rhPSMA-7.3; Fluorine F 18 Radiohybrid PSMA-7.3; Posluma

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Consensus detection rate	Reads will be completed for the positron emission tomography (PET)/computed tomography (CT) by three trained radiologist blinded to each other's read. Uptake values of rhPSMA-7.3 (POSLUMA) in the prostate bed and other sites (i.e. lymph nodes or bones) will be evaluated. Location and avidity (standardized uptake value) of all identified PET positive sites will be recorded (series/slice number). Consensus read will be determined as positive or negative at the patient level as the consensus of at least 2 of the 3 reading radiologists. Detection rates will be presented with 95% confidence intervals.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient level verified detection rates	Patient level verified detection rates will be assessed directly by histopathology or indirectly by secondary imaging or serial imaging with treatment response over the course of 2 years from study scan. Results will be reported in tabular format.	Up to 2 years
Change in management plan based on POSLUMA scan	The change in management plan based on POSLUMA scan will be assessed as no, minor, or major change as dictated at provider's discretion after POSLUMA scan. Decisions regarding the care of the patient following PET/CT will be made and change from the pre-scan clinical pathway will be recorded subjectively by the treating physician as none, minor or major. Minor changes would include changes in intended frequency of monitoring, modifications within a radiation treatment field. Major changes would include changing from observation to treatment, treatment to observation, extension or inclusion of a new radiation treatment field, extension or reduction in duration of or use of additional systemic medications. Changes in management plans will be reported as frequencies and percentages.	Up to 2 years

Collaborators and Investigators

• Sponsor: Northwestern University
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Ashley E Ross, Northwestern University

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2032

Study Registration Dates

• First Submitted: February 3, 2025
• First Submitted That Met QC Criteria: February 3, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 17, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Prostatic Neoplasms; Adenocarcinoma; Physiological Effects of Drugs; Protective Agents; Cariostatic Agents; Fluorides
• Other Study ID Numbers: NU 24U08 (Other Identifier: Northwestern University); P30CA060553 (U.S. NIH Grant/Contract); NCI-2024-09380 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); STU00222061

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.: No