Prostate Adenocarcinoma, Recurrent Prostate Carcinoma
Conditions
Brief summary
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
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.
Interventions
DRUGFurosemide
Given IV
OTHERF18-rhPSMA-7.3
Given IV
PROCEDUREPositron Emission Tomography
Undergo PET/CT scan
PROCEDUREComputed Tomography
Undergo PET/CT scan
Sponsors
National Cancer Institute (NCI)
Blue Earth Diagnostics
Emory University
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Bladder Activity as Measured by Bladder Standardized Uptake Value (SUV) Mean | Up to 2 weeks | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Bladder and Renal Activity (Kidney SUV) | Up to 2 weeks | Kidney SUV - 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). |
| Change in Bladder and Renal Activity (Bladder Volume, ML) | Up to 2 weeks | (Bladder Volume, ML) - 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). |
| Recurrent Disease Rate | Up to 2 weeks | 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). |
| Reader Confidence Score | 1 Month | 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 ( 1 - Definitely benign, 2- probably benign, 3 - equivocal, 4 - probably malignant, 5 - definitely malignant). This analysis will be descriptive, with summary statistics reported with and without furosemide. Variables will be summarized using frequencies and percentages. In our analysis, 1,2 (no) will be considered benign while 3,4,5 malignant (yes). A high Likert score indicates that the reader is confident that the finding on the imaging is cancer (worse outcome), while a low score indicates no cancer (better outcome). 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (furosemide, F-18 rhPSMA-7.3, PET-CT) Patients receive F-18 rhPSMA 7.3 tracer IV and then undergo PET-CT scans with and without furosemide IV on study.
Furosemide: Given IV
F18-rhPSMA-7.3: Given IV
Positron Emission Tomography: Undergo PET/CT scan
Computed Tomography: Undergo PET/CT scan | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Treatment (furosemide, F-18 rhPSMA-7.3, PET-CT) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 13 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Age, Continuous | 67.95 Years STANDARD_DEVIATION 8.17 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Region of Enrollment United States | 20 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 0 / 10 | 0 / 10 | 1 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 |
Outcome results
Primary
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).
Time frame: Up to 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment (furosemide, F-18 rhPSMA-7.3, PET-CT) | Change in Bladder Activity as Measured by Bladder Standardized Uptake Value (SUV) Mean | 3.9 SUV | Standard Deviation 3.71 |
| Without furosemide | Change in Bladder Activity as Measured by Bladder Standardized Uptake Value (SUV) Mean | 20.64 SUV | Standard Deviation 31.5 |
Secondary
Change in Bladder and Renal Activity (Bladder Volume, ML)
(Bladder Volume, ML) - 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).
Time frame: Up to 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment (furosemide, F-18 rhPSMA-7.3, PET-CT) | Change in Bladder and Renal Activity (Bladder Volume, ML) | 300.22 ML | Standard Deviation 151.3 |
| Without furosemide | Change in Bladder and Renal Activity (Bladder Volume, ML) | 147.69 ML | Standard Deviation 172.31 |
Secondary
Change in Bladder and Renal Activity (Kidney SUV)
Kidney SUV - 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).
Time frame: Up to 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment (furosemide, F-18 rhPSMA-7.3, PET-CT) | Change in Bladder and Renal Activity (Kidney SUV) | 24.87 SUV | Standard Deviation 7.95 |
| Without furosemide | Change in Bladder and Renal Activity (Kidney SUV) | 27.12 SUV | Standard Deviation 8.46 |
Secondary
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 ( 1 - Definitely benign, 2- probably benign, 3 - equivocal, 4 - probably malignant, 5 - definitely malignant). This analysis will be descriptive, with summary statistics reported with and without furosemide. Variables will be summarized using frequencies and percentages. In our analysis, 1,2 (no) will be considered benign while 3,4,5 malignant (yes). A high Likert score indicates that the reader is confident that the finding on the imaging is cancer (worse outcome), while a low score indicates no cancer (better outcome). 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.
Time frame: 1 Month
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (furosemide, F-18 rhPSMA-7.3, PET-CT) | Reader Confidence Score | Pelvis-Agree (No) (Low Lickert Score 1-2) | 1 participants |
| Treatment (furosemide, F-18 rhPSMA-7.3, PET-CT) | Reader Confidence Score | Prostate Agree (No) (Low Lickert Score 1-2) | 10 participants |
| Treatment (furosemide, F-18 rhPSMA-7.3, PET-CT) | Reader Confidence Score | Extra-Prostate-Agree (Yes) (High Lickert Score 3-5) | 15 participants |
| Treatment (furosemide, F-18 rhPSMA-7.3, PET-CT) | Reader Confidence Score | Prostate Agree (Yes) (High Lickert Score 3-5) | 10 participants |
| Treatment (furosemide, F-18 rhPSMA-7.3, PET-CT) | Reader Confidence Score | Extra-Prostate-Agree (No) (Low Lickert Score 1-2) | 5 participants |
| Treatment (furosemide, F-18 rhPSMA-7.3, PET-CT) | Reader Confidence Score | Pelvis-Agree (Yes) (High Lickert Score 3-5) | 19 participants |
| Without furosemide | Reader Confidence Score | Extra-Prostate-Agree (No) (Low Lickert Score 1-2) | 5 participants |
| Without furosemide | Reader Confidence Score | Prostate Agree (Yes) (High Lickert Score 3-5) | 9 participants |
| Without furosemide | Reader Confidence Score | Prostate Agree (No) (Low Lickert Score 1-2) | 11 participants |
| Without furosemide | Reader Confidence Score | Pelvis-Agree (No) (Low Lickert Score 1-2) | 1 participants |
| Without furosemide | Reader Confidence Score | Extra-Prostate-Agree (Yes) (High Lickert Score 3-5) | 15 participants |
| Without furosemide | Reader Confidence Score | Pelvis-Agree (Yes) (High Lickert Score 3-5) | 19 participants |
Secondary
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).
Time frame: Up to 2 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (furosemide, F-18 rhPSMA-7.3, PET-CT) | Recurrent Disease Rate | Prostate bed - Negative (No recurrence detected) | 3 Participants |
| Treatment (furosemide, F-18 rhPSMA-7.3, PET-CT) | Recurrent Disease Rate | Prostate bed - Positive (Recurrence detected) | 17 Participants |
| Treatment (furosemide, F-18 rhPSMA-7.3, PET-CT) | Recurrent Disease Rate | Pelvic - Negative (No recurrence detected) | 18 Participants |
| Treatment (furosemide, F-18 rhPSMA-7.3, PET-CT) | Recurrent Disease Rate | Pelvic - Positive (Recurrence detected) | 2 Participants |
| Treatment (furosemide, F-18 rhPSMA-7.3, PET-CT) | Recurrent Disease Rate | Extra pelvic - Negative (No recurrence detected) | 16 Participants |
| Treatment (furosemide, F-18 rhPSMA-7.3, PET-CT) | Recurrent Disease Rate | Extra pelvic - Positive (Recurrence detected) | 4 Participants |
| Treatment (furosemide, F-18 rhPSMA-7.3, PET-CT) | Recurrent Disease Rate | Patient level - Negative (No recurrence detected) | 2 Participants |
| Treatment (furosemide, F-18 rhPSMA-7.3, PET-CT) | Recurrent Disease Rate | Patient level - Positive (Recurrence detected) | 18 Participants |
| Without furosemide | Recurrent Disease Rate | Patient level - Positive (Recurrence detected) | 15 Participants |
| Without furosemide | Recurrent Disease Rate | Prostate bed - Negative (No recurrence detected) | 8 Participants |
| Without furosemide | Recurrent Disease Rate | Extra pelvic - Negative (No recurrence detected) | 16 Participants |
| Without furosemide | Recurrent Disease Rate | Prostate bed - Positive (Recurrence detected) | 12 Participants |
| Without furosemide | Recurrent Disease Rate | Patient level - Negative (No recurrence detected) | 5 Participants |
| Without furosemide | Recurrent Disease Rate | Pelvic - Negative (No recurrence detected) | 17 Participants |
| Without furosemide | Recurrent Disease Rate | Extra pelvic - Positive (Recurrence detected) | 4 Participants |
| Without furosemide | Recurrent Disease Rate | Pelvic - Positive (Recurrence detected) | 3 Participants |