Comparison of 18F-rhPSMA-7.3 PET/CT With and Without Furosemide in Biochemical Recurrence of Prostate Cancer

Study Overview
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Brief Summary
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This phase II trial evaluates Fluorine-18 radiohybrid prostate-specific membrane antigen (18F- rhPSMA)-7.3 positron emission tomography (PET)/computed tomography (CT) scans with and without furosemide for the reduction of bladder activity in patients with prostate cancer that has come back (recurrent) based on elevated levels of prostate-specific antigen (PSA) in the blood (biochemical) after prostate surgery (prostatectomy). Furosemide is a diuretic substance that increases the urine flow into the bladder, thereby decreasing the level of radioactivity within the bladder, which may help to see any abnormal areas that could be masked by the radioactivity within the bladder. PET is an established imaging technique that utilizes small amounts of radioactivity attached to very minimal amounts of tracer, in the case of this research, rhPSMA ligand. CT utilizes x-rays that traverse body from the outside. CT images provide an exact outline of organs and potential inflammatory tissue where it occurs in patient's body. Adding furosemide to 18F-rhPSMA 7.3 PET/CT scans may help to better detect and treat patients with biochemically recurrent prostate cancer.

Detailed Description
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PRIMARY OBJECTIVE: I. To determine if administering 20 mg furosemide intravenously (IV) at the time of radiotracer injection significantly reduces bladder activity compared with the same patient scanned without furosemide as internal control. SECONDARY OBJECTIVES: I. To compare detection rates of recurrent disease in blinded interpretations between the furosemide and non-furosemide 18FrhPSMA-7.3 PET/CT scans, with patients serving as their own internal controls. II. To compare reader confidence in identifying prostate bed and other recurrent lesions on a 18F-rhPSMA-7.3 PET/CT with furosemide compared with 18F-rhPSMA-7.3 PET/CT without furosemide. OUTLINE: Patients receive 18F-rhPSMA 7.3 tracer IV and then undergo PET-CT scans with and without furosemide IV on study.

Official Title
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Strategy to Reduce Bladder Activity With RhPSMA 7.3: Comparison of 18F-RhPSMA 7.3 PET/CT With and Without Furosemide in Biochemical Recurrence of Prostate Cancer

Conditions
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Prostate Adenocarcinoma, Recurrent Prostate Carcinoma

Intervention / Treatment
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* Drug: Furosemide
* Other: F18-rhPSMA-7.3
* Procedure: Positron Emission Tomography
* Procedure: Computed Tomography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adenocarcinoma of the prostate, post-prostatectomy Biochemical recurrence of prostate cancer following radical prostatectomy (RP) with or without adjuvant or salvage therapy: PSA >= 0.2 ng/mL followed by a subsequent confirmatory PSA value >= 0.2 ng/mL Age over 18 Ability to provide written informed consent Patients with standard of care creatinine =< 1.3 mg/dL performed within 90 days prior to enrollment Exclusion Criteria: - Inability to undergo 18F-rhPSMA PET-CT, contraindications to furosemide or urinary incontinence

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (furosemide, F-18 rhPSMA-7.3, PET-CT)<br>Patients receive F-18 rhPSMA 7.3 tracer IV and then undergo PET-CT scans with and without furosemide IV on study. | Drug: Furosemide<br>* Given IV<br>* Other names: 54-31-9, FRS, Furosemide, FUROSEMIDE, Lasix, Lasix, LB 502, LB-502, LB-502, SK-Furosemide;Other: F18-rhPSMA-7.3<br>* Given IV<br>* Other names: (18F)-rhPSMA-7.3,18F-rhPSMA-7.3,18FrhPSMA-7.3,2305081-64-3,F-18-rhPSMA-7.3,FLOTUFOLASTAT F-18, Fluorine F18 radiohybrid PSMA-7.3, Fluorine F18 rhPSMA-7.3, Fluorine-18 rhPSMA-7.3, rhPSMA-7.3(18F);Procedure: Positron Emission Tomography<br>* Undergo PET/CT scan<br>* Other names: Medical Imaging,Positron Emission Tomography, PET, PET SCAN;Procedure: Computed Tomography<br>* Undergo PET/CT scan<br>* Other names: CAT, CAT Scan, CAT scan, CAT Scan,Computed Axial Tomography,Computed Tomography, Computerized Axial Tomography;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in bladder activity as measured by bladder standardized uptake value (SUV) mean | Change in bladder SUV mean will be assessed using a paired t-test, or using a non-parametric equivalent such as a Wilcoxon signed rank test. Descriptively, change in bladder SUV mean will be reported for those administered 20 mg furosemide intravenously (IV) at the time of radiotracer injection first (group A), and those administered 20mg furosemide IV at the time of radiotracer injection second (group B). | Up to 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in bladder and renal activity | Change in bladder and renal activity will be assessed using paired t-tests, or using non-parametric equivalents such as a Wilcoxon signed rank tests. Descriptively, bladder and renal activity will be reported for those administered 20 mg furosemide IV at the time of radiotracer injection first (group A), and those administered 20 mg furosemide IV at the time of radiotracer injection second (group B). | Up to 2 weeks | 
| Recurrent disease rate | Defined as presence of unequivocal soft tissue radiotracer uptake that is characteristic of malignancy in the prostate bed and/or surrounding soft tissues and within pelvic lymph nodes. Recurrent disease rates will be compared (furosemide versus non-furosemide flotufolastat F-18 radiohybrid prostate-specific membrane antigen (18F-rhPSMA)-7.3 positron emission tomography (PET) scans using McNemar's tests. Rates will be reported, along with 95% exact confidence intervals using the Clopper-Pearson method. Descriptively, recurrent disease rate will be reported for those administered 20 mg furosemide IV at the time of radiotracer injection first (group A), and those administered 20 mg furosemide IV at the time of radiotracer injection second (group B). | Up to 2 weeks | 
| Reader confidence score | The readers' confidence in identifying prostate bed, pelvic and retroperitoneal nodal disease and other recurrence on 18F-rhPSMA-7.3 PET/computed tomography (CT) with furosemide compared with the 18F-rhPSMA-7.3 PET/CT without furosemide will be scored using a 5-point Likert scale. This analysis will be descriptive, with summary statistics reported with and without furosemide. Continuous variables will be summarized using mean, median, interquartile range, standard deviation, and min/max. Categorical variables will be summarized using frequencies and percentages. All tests will be two-sided with an alpha level of 0.05, unless otherwise noted. Statistical analysis will be conducted using SAS 9.4. | Up to 4 years |