Study of 18F-DCFPyL PET/CT Imaging in Patients With Prostate Cancer

Study Overview
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Brief Summary
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This study evaluates the safety and diagnostic performance of 18F-DCFPyL Injection in patients with at least high risk prostate cancer who are planned for radical prostatectomy with lymphadenectomy (Cohort A) or in patients with locally recurrent or metastatic disease willing to undergo biopsy (Cohort B). Cohort B is complete and no longer recruiting subjects.

Official Title
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A PrOspective Phase 2/3 Multi-Center Study of 18F-DCFPyL PET/CT Imaging in Patients With PRostate Cancer: Examination of Diagnostic AccuracY (OSPREY)

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: 18F-DCFPyL Injection
* Diagnostic Test: PET/CT imaging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed adenocarcinoma of the prostate. Subjects provide signed informed consent and confirm that they are able and willing to comply with all protocol requirements. Cohort A Only: At least high risk prostate cancer defined by NCCN Guidelines Version 3.2016 (clinical stage ≥T3a or PSA >20 ng/mL or Gleason score ≥8). Scheduled or planned radical prostatectomy with PLND. Cohort B Only: [Enrollment is complete; No longer recruiting subjects] Radiologic evidence of local recurrence or new or progressive metastatic disease demonstrated on anatomical imaging (CT, MRI, or ultrasound), whole-body bone scan (99m-Tc-MDP or Na-18F) within 4 weeks of enrollment. If prior treatment with radiation or ablative therapy, evidence of recurrence outside the confines of prior treated site(s) is needed. Scheduled or planned percutaneous biopsy of at least one amenable lesion. Exclusion Criteria: Subjects administered any high energy (>300 KeV) gamma-emitting radioisotope within five physical half-lives, or any IV iodinated contrast medium within 24 hours, or any high density oral contrast medium (oral water contrast is acceptable) within 5 days, prior to study drug injection. Subjects with any medical condition or other circumstance that, in the opinion of the investigator, compromise obtaining reliable data, achieving study objectives, or completion. Cohort A Only: Patients with prior androgen deprivation therapy or any investigational neoadjuvant agent or intervention Cohort B Only: [Enrollment is Complete; No longer recruiting subjects] Prior radiation or ablative therapy to intended site of biopsy, if within the prostate bed Initiation of new therapy for recurrent and/or progressive metastatic disease since radiographic documentation of recurrence/progression.

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: 18F-DCFPyL Injection<br>9±1 mCi (333±37 MBq) IV injection of 18F-DCFPyL | Drug: 18F-DCFPyL Injection<br>* A single dose of 9±1 mCi (333±37 MBq) IV injection of 18F-DCFPyL<br>* Other names: PyL;Diagnostic Test: PET/CT imaging<br>* PET/CT imaging will be acquired 1-2 hours post-PyL injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Specificity of 18F-DCFPyL PET/CT Imaging to Detect Metastatic Prostate Cancer Within the Pelvic Lymph Nodes Relative to Histopathology in High Risk Prostate Cancer Participants (Cohort A) | The primary analysis in Cohort A will test the co-primary endpoints of sensitivity and specificity of 18F-DCFPyL PET/CT imaging relative to histopathology for metastatic disease in pre-prostatectomy patients. For each co-primary endpoint there will be three independent imaging readers. At least two of the three readers must reject the null hypothesis for specificity to be deemed a success. If specificity is a success, then the same two readers need to reject the null hypothesis for sensitivity to reach overall success of the primary endpoint. | Within 28 days of imaging, radical prostatectomy with pelvic lymph node dissection will occur. | 
| Sensitivity of 18F-DCFPyL PET/CT Imaging to Detect Metastatic Prostate Cancer Within the Pelvic Lymph Nodes Relative to Histopathology in High Risk Prostate Cancer Participants (Cohort A) | The primary analysis in Cohort A will test the co-primary endpoints of sensitivity and specificity of 18F-DCFPyL PET/CT imaging relative to histopathology for metastatic disease in pre-prostatectomy patients. For each co-primary endpoint there will be three independent imaging readers. At least two of the three readers must reject the null hypothesis for specificity to be deemed a success. If specificity is a success, then the same two readers need to reject the null hypothesis for sensitivity to reach overall success of the primary endpoint. | Within 28 days of imaging, radical prostatectomy with pelvic lymph node dissection will occur. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Shift From Baseline in Selected Hematology Laboratory Values at Follow-up (Safety Outcome Measure) | Shifts from baseline to worst post-baseline visit for hematology laboratory values for all participants included in the Safety Set. The Safety Set includes all participants who received any amount of 18F-DCFPyL. Data are presented for participants in Cohort A and Cohort B. | From time of screening (baseline) until pre-surgery/biopsy (within 28 days post-study drug dosing). | 
| Shift From Baseline in Selected Clinical Chemistry Laboratory Values at Follow-up (Safety Outcome Measure) | Shifts from baseline to worst post-baseline visit for clinical chemistry laboratory values for all participants included in the Safety Set. The Safety Set includes all participants who received any amount of 18F-DCFPyL. Data are presented for participants in Cohort A and Cohort B. | From time of screening (baseline) until pre-surgery/biopsy (within 28 days post-study drug dosing). | 
| Changes From Baseline in Electrocardiogram (ECG) Parameters (Safety Outcome Measure) |  | Changes in ECG pre-drug dosing and within 1-2 hours post-dosing | 
| Mean Changes From Baseline in Blood Pressure Post 18F-DCFPyL Dosing (Safety Outcome Measure) |  | Measured at two intervals on the day of dosing, pre-dosing (baseline) and post-dosing/pre-imaging. | 
| Mean Change From Baseline in Heart Rate Post 18F-DCFPyL Dosing (Safety Outcome Measure) |  | Measured at two intervals on the day of dosing, pre-dosing (baseline) and post-dosing/pre-imaging. | 
| Mean Change From Baseline in Respiration Rate Post 18F-DCFPyL Dosing (Safety Outcome Measure) |  | Measured at two intervals on the day of dosing, pre-dosing (baseline) and post-dosing/pre-imaging. | 
| Mean Change From Baseline in Temperature Post 18F-DCFPyL Dosing (Safety Outcome Measure) |  | Measured at two intervals on the day of dosing, pre-dosing (baseline) and post-dosing/pre-imaging. | 
| Sensitivity of 18F-DCFPyL PET/CT Imaging to Detect Prostate Cancer Within Sites of Metastasis or Local Recurrence Relative to Histopathology in Participants With Recurrent or Metastatic Prostate Cancer (Cohort B) | Sensitivity (True Positive rate) measures the proportion of positives that are correctly identified (i.e., the proportion of those who have some condition (affected) who are correctly identified as having the condition). | Within 28 days of 18F-DCFPyL PET/CT imaging, conventional image-guided biopsy occurred. | 
| Comparison of Detection Rates for Lesion Counts By Location and Overall Between 18F-DCFPyL PET/CT and Conventional Imaging | The number of lesions detected on imaging categorized as bone, visceral/soft tissue, lymph nodes, and the prostate gland will be determined by each of the central imaging core lab independent readers. The sum of lesions per participant per tissue type and overall will be computed for each participant based on each reader's lesion count. This will be calculated from the 18F-DCFPyL PET/CT scan results as well as the conventional imaging results. | Within 1-2 hours of 18F-DCFPyL dosing, a whole body PET/CT scan will be taken | 
| Positive Predictive Value (PPV) of 18F-DCFPyL PET/CT to Predict Prostate Cancer Within the Prostate Gland of High Risk Prostate Cancer Participants (Cohort A) | Positive Predictive Value (PPV) is based on a 18F-DCFPyL PET/CT image result and a histopathology result. The PPV is determined from the number of true positives (positive 18F-DCFPyL image and a positive histopathology result for prostate cancer) divided by the number of participants with a positive 18F-DCFPyL image. | Within 28 days of imaging, radical prostatectomy with pelvic lymph node dissection will occur. | 
| Negative Predictive Value (NPV) of 18F-DCFPyL PET/CT to Predict Prostate Cancer Within the Prostate Gland of High Risk Prostate Cancer Participants (Cohort A) | Negative Predictive Value (NPV) is based on a 18F-DCFPyL PET/CT image result and a histopathology result. The NPV is determined from the number of true negatives (negative 18F-DCFPyL image and a negative histopathology result for prostate cancer) divided by the number of participants with a negative 18F-DCFPyL image. | Within 28 days of imaging, radical prostatectomy with pelvic lymph node dissection will occur. | 
| Positive Predictive Value (PPV) of 18F-DCFPyL PET/CT to Predict Prostate Cancer Within the Lymph Nodes of High Risk Prostate Cancer Participants (Cohort A) | Positive Predictive Value (PPV) is based on a 18F-DCFPyL PET/CT image result and a histopathology result. The PPV is determined from the number of true positives (positive 18F-DCFPyL image and a positive histopathology result for prostate cancer) divided by the number of participants with a positive 18F-DCFPyL image. | Within 28 days of imaging, radical prostatectomy with pelvic lymph node dissection will occur. | 
| Negative Predictive Value (NPV) of 18F-DCFPyL PET/CT to Predict Prostate Cancer Within the Lymph Nodes of High Risk Prostate Cancer Participants (Cohort A) | Negative Predictive Value (NPV) is based on a 18F-DCFPyL PET/CT image result and a histopathology result. The NPV is determined from the number of true negatives (negative 18F-DCFPyL image and a negative histopathology result for prostate cancer) divided by the number of participants with a negative 18F-DCFPyL image. | Within 28 days of imaging, radical prostatectomy with pelvic lymph node dissection will occur. | 
| Positive Predictive Value (PPV) of 18F-DCFPyL PET/CT Imaging to Predict Prostate Cancer Within Sites of Local Recurrence and Other Metastatic Lesions in Participants With Recurrent or Metastatic Prostate Cancer (Cohort B) | Positive Predictive Value (PPV) is based on a 18F-DCFPyL PET/CT image result and a histopathology result. The PPV is determined from the number of true positives (positive 18F-DCFPyL image and a positive histopathology result for prostate cancer) divided by the number of participants with a positive 18F-DCFPyL PET/CT image. | Within 28 days of 18F-DCFPyL PET/CT imaging, conventional image-guided biopsy will occur. | 
| Peak Plasma Concentration (Cmax) of 18F-DCFPyL in a Subset of Participants |  | Samples were collected at 0, 5, 15, 30, 60, 120, 240, 360, and 480 minutes after administration of 18F-DCFPyL. | 
| Area Under the Plasma Concentration Versus Time Curve (AUC) of 18F-DCFPyL in a Subset of Participants |  | Samples were collected at 0, 5, 15, 30, 60, 120, 240, 360, and 480 minutes after administration of 18F-DCFPyL. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diagnostic, Imaging, 2301, PET/CT, PyL, PSMA, radical prostatectomy, metastatic prostate cancer, recurrent prostate cancer