Diagnostic Utility of rhPSMA-7.3 (18F) PET/CT in Men With Prostate Cancer on Active Surveillance

NCT ID: NCT07285057

Last Updated: 2025-12-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-12-31

Study Completion Date

2027-05-01

Brief Summary

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This investigator-initiated, prospective study evaluates the diagnostic utility of rhPSMA-7.3 (¹⁸F) PET/CT (flotufolastat F18, marketed as POSLUMA®) in men with biopsy-proven, low-risk or favorable intermediate-risk prostate cancer managed with active surveillance. The study aims to determine whether the addition of PSMA-based PET/CT to standard multiparametric MRI (mpMRI) improves detection of clinically significant prostate cancer compared to MRI alone. Eligible participants will undergo rhPSMA-7.3 (¹⁸F) PET/CT and mpMRI prior to confirmatory prostate biopsy. Biopsies will target areas identified on MRI, PET/CT, or both, and histopathologic outcomes will serve as the reference standard. The study will assess lesion-level concordance between PET/CT, MRI, and pathology, and evaluate the predictive value of PET/CT for disease upgrading. Approximately 120 participants will be enrolled at Mount Sinai Hospital over 12 months. Study participation will involve one imaging visit, one confirmatory biopsy, and follow-up through review of clinical results. There is minimal risk to participants beyond standard diagnostic procedures. The study is funded jointly by the Icahn School of Medicine at Mount Sinai and Blue Earth Diagnostics, which provides the imaging agent flotufolastat F18 and technical support.

Detailed Description

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This investigator-initiated, single-center, prospective study aims to evaluate the diagnostic utility of rhPSMA-7.3 (¹⁸F) PET/CT (flotufolastat F18, marketed as POSLUMA®) in detecting clinically significant prostate cancer (csPCa) among men on active surveillance for low-risk or favorable intermediate-risk prostate cancer.

Background and Rationale: Active surveillance (AS) is the preferred management strategy for carefully selected men with low-risk and favorable intermediate-risk prostate cancer, balancing the avoidance of overtreatment against the need to identify disease progression early. Current surveillance strategies rely on serial PSA monitoring, digital rectal examination, mpMRI, and confirmatory biopsies. However, mpMRI can miss or underestimate clinically significant lesions, particularly those in the anterior or transitional zones. Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer cells and can be visualized using PET/CT imaging with radiolabeled PSMA ligands. The next-generation tracer rhPSMA-7.3 (¹⁸F), or flotufolastat F18, has demonstrated improved image resolution, favorable kinetics, and low urinary excretion compared to earlier PSMA ligands. Incorporating PSMA PET/CT into the active surveillance pathway may identify occult or higher-grade disease not detected by MRI, improving risk stratification and treatment decision-making.

Study Objectives: The primary objective of the study is to determine whether the addition of rhPSMA-7.3 (¹⁸F) PET/CT to standard mpMRI improves detection of clinically significant prostate cancer (ISUP Grade Group ≥2) in men on active surveillance.

Secondary objectives include: Comparing lesion-level concordance between PET/CT, mpMRI, and histopathology. Evaluating the predictive value of PET SUVmax for detecting clinically significant disease. Assessing diagnostic performance metrics (sensitivity, specificity, PPV, NPV) for PET/CT versus MRI. Quantifying the proportion of patients reclassified (i.e., upgraded or transitioned from AS to definitive treatment) based on PET/CT findings.

Exploratory endpoints include: Association between PET quantitative parameters (SUVmax, lesion volume) and PSA density. Characterization of PET-only lesions not visualized on MRI. Correlation of PET/CT findings with adverse pathological features (ECE, SVI, cribriform/intraductal carcinoma) at biopsy or surgery. Evaluation of lesion-level changes in SUVmax and volume in patients who undergo repeat PET/CT.

Study Design: This is a prospective, single-arm diagnostic utility study. Approximately 120 participants with histologically confirmed low-risk or favorable intermediate-risk prostate cancer managed with active surveillance will be enrolled at Mount Sinai Hospital. All participants will undergo both mpMRI and rhPSMA-7.3 (¹⁸F) PET/CT prior to confirmatory biopsy. Imaging data will be reviewed by genitourinary radiologists and nuclear medicine physicians blinded to each other's findings. Lesions will be recorded according to standardized templates (e.g., PIRADS 2.1 for MRI and SUV-based mapping for PET/CT). Targeted biopsies will include MRI-positive, PET-positive, and fusion (concordant) targets, as well as systematic cores as per institutional protocol. Histopathology will serve as the reference standard for correlation. The study involves one PET/CT visit, one confirmatory biopsy, and up to three follow-up visits within 12 months.

Risks and Benefits: Risks include exposure to low-dose radiation comparable to standard diagnostic imaging, and expected biopsy-related discomfort such as pain, bleeding, infection, or transient urinary symptoms. Rare allergic reactions to flotufolastat F18 and mild emotional stress associated with imaging or awaiting results are possible but uncommon. There may be no direct benefit to participants. However, rhPSMA-7.3 (¹⁸F) PET/CT may help identify previously undetected higher-grade disease, leading to earlier or more appropriate treatment. The findings could improve future management of men on active surveillance.

Statistical Considerations: Diagnostic accuracy metrics will be analyzed at both lesion and patient levels using confirmatory biopsy as the gold standard. ROC analysis will determine SUVmax thresholds for predicting clinically significant disease. Concordance between PET and MRI findings will be evaluated with Cohen's kappa and McNemar's test. Sample size (n=120) is based on expected detection differences between PET/CT and MRI with 80% power and alpha=0.05.

Study Oversight: This study is conducted under the oversight of the Mount Sinai Program for the Protection of Human Subjects (PPHS) and complies with FDA regulations for IND-exempt studies involving FDA-approved radiopharmaceuticals (21 CFR 312.2(b)(1)). The study is jointly funded by the Icahn School of Medicine at Mount Sinai and Blue Earth Diagnostics. Mount Sinai is the study sponsor and holds regulatory responsibility. Blue Earth Diagnostics provides the imaging agent flotufolastat F18 (POSLUMA®), technical support, and partial financial support. Data management and analysis will be conducted internally at Mount Sinai. No external contract research organization (CRO) or vendor (e.g., Parexel) will manage study data.

Expected Duration: Enrollment start: November 2025 Primary completion: May 2027 (final confirmatory biopsy) Study completion: November 2027 (data lock and analysis)

Potential Impact: This study may validate the clinical role of rhPSMA-7.3 (¹⁸F) PET/CT in improving detection of clinically significant prostate cancer during active surveillance. The results may support integration of PSMA-targeted PET imaging into future diagnostic pathways, minimizing unnecessary biopsies and improving individualized management.

Conditions

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Prostatic Neoplasms Prostate Cancer Prostate Adenocarcinoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

This is a single-arm, prospective diagnostic imaging study in which all enrolled participants will undergo rhPSMA-7.3 (¹⁸F) PET/CT and standard multiparametric MRI prior to confirmatory prostate biopsy. Each participant serves as an own control for within-patient comparison of imaging modalities. No randomization or separate intervention arms are used.
Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

This is an open-label diagnostic imaging study. Neither participants nor investigators are blinded to the imaging procedures. However, imaging interpretation will be performed independently - PET/CT scans will be reviewed by nuclear medicine physicians blinded to MRI findings, and MRI scans will be reviewed by radiologists blinded to PET/CT results. Pathologists evaluating biopsy specimens will be blinded to imaging results to minimize interpretation bias.

Study Groups

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rhPSMA-7.3 (18F) PET/CT Imaging

Participants in this arm will undergo rhPSMA-7.3 (¹⁸F) PET/CT (flotufolastat F18, POSLUMA®) imaging and standard multiparametric MRI prior to confirmatory prostate biopsy. All participants receive the same imaging procedures; there are no control or comparison arms.

Group Type EXPERIMENTAL

rhPSMA-7.3 (18F) PET/CT Imaging (Flotufolastat F18, POSLUMA®)

Intervention Type RADIATION

Participants will undergo a single rhPSMA-7.3 (¹⁸F) PET/CT scan using flotufolastat F18 (POSLUMA®), an FDA-approved PSMA-targeted radiotracer. The radiotracer will be administered intravenously at the standard diagnostic dose prior to PET/CT image acquisition. The scan will be performed according to institutional imaging protocols, approximately 50-70 minutes post-injection.

Flotufolastat F18

Intervention Type DRUG

An FDA-approved PSMA-targeted radiotracer. The radiotracer will be administered intravenously at the standard diagnostic dose prior to PET/CT image acquisition.

Interventions

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rhPSMA-7.3 (18F) PET/CT Imaging (Flotufolastat F18, POSLUMA®)

Participants will undergo a single rhPSMA-7.3 (¹⁸F) PET/CT scan using flotufolastat F18 (POSLUMA®), an FDA-approved PSMA-targeted radiotracer. The radiotracer will be administered intravenously at the standard diagnostic dose prior to PET/CT image acquisition. The scan will be performed according to institutional imaging protocols, approximately 50-70 minutes post-injection.

Intervention Type RADIATION

Flotufolastat F18

An FDA-approved PSMA-targeted radiotracer. The radiotracer will be administered intravenously at the standard diagnostic dose prior to PET/CT image acquisition.

Intervention Type DRUG

Other Intervention Names

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POSLUMA®

Eligibility Criteria

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Inclusion Criteria

* Male participants aged ≥18 years.
* Histologically confirmed diagnosis of prostate adenocarcinoma.
* Classified as low-risk or favorable intermediate-risk prostate cancer according to NCCN criteria: Low-risk: Grade Group 1, PSA \<10 ng/mL, cT1-T2a Favorable intermediate-risk: Grade Group 2, PSA 10-20 ng/mL, cT2b-c Currently managed with active surveillance.
* Able and willing to undergo rhPSMA-7.3 (¹⁸F) PET/CT imaging, mpMRI, and confirmatory prostate biopsy.
* Able to provide written informed consent.

Exclusion Criteria

* A history of other active malignancy within the last 5 years, except for non-melanoma skin cancer.
* Contraindication to 3-T mpMRI.
* Significant intercurrent morbidity\*\* limiting compliance with study protocols.

\*\* Significant intercurrent morbidity refers to a substantial medical condition or complication that arises during a study or treatment, which is severe enough to impact the patient's participation, treatment outcomes, or overall prognosis. These conditions may be unrelated to the primary disease but can influence clinical decision-making, treatment efficacy, and patient safety. Examples include major infections, cardiovascular events, organ failure, or significant worsening of pre-existing comorbidities (https://doi.org/10.1016/S1053-4296(03)00031-6).
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to Agent(s) or other agents used in study.
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Blue Earth Diagnostics

INDUSTRY

Sponsor Role collaborator

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role lead

Responsible Party

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Ashutosh Kumar Tewari

Professor and System Chair

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ashutosh Tewari

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

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Mount Sinai Hospital / Icahn School of Medicine at Mount Sinai

New York, New York, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Neeraja Tillu, MBBS, MS, MCh.

Role: CONTACT

646-799-1870

Monali Fatterpekar, PhD

Role: CONTACT

Facility Contacts

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Neeraja Tillu, MBBS, MS, MCh

Role: primary

646-799-1870

Monali Fatterpekar

Role: backup

Other Identifiers

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STUDY-25-00518

Identifier Type: -

Identifier Source: org_study_id