Clinical trial NCT02523924
Conditions: Adenocarcinoma of the Prostate
Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Start date: 2015-06-02; Completion date: 2019-03-04
Enrollment: 50 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This pilot study aims to investigate the diagnostic utility of 18F-DCFPyL, a novel low-molecular weight PSMA PET/CT imaging agent, in men with an elevated PSA following radical prostatectomy.

Detailed description:
18F-DCFPyL is a novel low-molecular weight PSMA imaging agent. A recent study of patients with metastatic prostate cancer found that PSMA PET/CT identified more sites of disease than conventional imaging with CT, MRI and bone scan. In this study we aim to investigate 18F-DCFPyL PET/CT in patients with an elevated PSA following radical prostatectomy. During the course of this study, patients will undergo two 18F-DCPyL PET/CT scans. The first scan will take place within 45 days of staging imaging and the second will take place following six months of standard of care therapy.

Arms: arm 1: Men with an elevated PSA following radical prostatectomy imaged with 18F-DCFPyL PET/CT
Interventions: intervention 1: 18F-DCFPyL
Intervention descriptions: intervention 1: 18F-DCFPyL PET/CT

Protocol documents:
Prot_SAP_000.pdf: 
NCT02523924 
Pilot Study of 18F-DCFPyL PET/CT in the Evaluation of Men with an Elevated 
PSA Following Radical Prostatectomy 
 
 
 
Principal Investigator:  
Kenneth J. Pienta, M.D.1 
 
 
Co-Investigators:     
Michael A. Gorin, M.D.1 
 
Bruce Trock, Ph.D.1  
 
Martin G. Pomper, M.D., Ph.D.2 
 
 
Steve P. Rowe, M.D., Ph.D.2 
 
Zsolt Szabo, M.D., Ph.D.2 
 
Phouc Tran, M.D., Ph.D.3 
 
Curtiland Deville, M.D.3 
 
Esther Mena Gonzalez, M.D.2 
 
 
Affiliations: 
1Depatment of Urology and The James Buchanan Brady 
Urological Institute 
 
2The Russell H. Morgan Department of Radiology and 
Radiological Science, Division of Nuclear Medicine 
 
3Department of Radiation Oncology and Molecular Radiation 
Sciences 
 
 
Johns Hopkins University School of Medicine 
 
Baltimore, MD, USA 
 
 
Version Date: 
February 21, 2017 
 
 
 
 
 
 
 
 


2 
 
 
 
1. STUDY SUMMARY 
 
PROTOCOL TITLE 
Pilot Study of 18F-DCFPyL PET/CT in the 
Evaluation of Men with an Elevated PSA Following 
Radical Prostatectomy 
IRB NUMBER 
IRB00062296 
IND NUMBER 
121064   
INVESTIGATIONAL AGENT 
18F-DCFPyL 
PATIENT POPULATION 
Men with an elevated PSA level following radical 
prostatectomy for adenocarcinoma of the prostate 
SAMPLE SIZE 
N = 50 
ENDPOINTS 
 Description of the number and location of 
putative sites of metastatic disease as 
determined by 18F-DCFPyL PET/CT 
 
 Correlation of findings on 18F-DCFPyL PET/CT 
with those found on conventional imaging 
 
 Correlation of findings on 18F-DCFPyL PET/CT 
with tissue histology and PSMA expression of 
biopsied/resected pathology specimens 
 
 Assessment of treatment response by 18F-
DCFPyL PET/CT following 6 months of 
management per the treating physician 
 
 Correlation of 18F-DCFPyL PET/CT findings with 
PSA levels and time to disease progression 
 
 
 


3 
 
 
 
2. STUDY SCHEMA 
 
 
 
 
 
Men with an Elevated PSA Following Radical 
Prostatectomy 
Screening Assessment 
Patient Registered into Study 
Informed Consent Obtained 
Study Completion 
18F-DCFPyL PET/CT 
Management per the Treating  
Physician x 6 Months 
18F-DCFPyL PET/CT 


4 
 
 
 
3. BACKGROUND & RATIONALE 
 
Prostate cancer represents the most common non-dermatologic malignancy in men, with an 
estimated 235,000 new cases diagnosed annually in the United States.1 At initial presentation, 
the majority of cases are organ-confined2,3 and will be adequately treated with radiation therapy 
or radical prostatectomy4. Following local treatment, nearly 20% of men will experience a 
biochemical recurrence and up to half of these men will go on to develop overt metastatic 
disease.5-7 Additionally, a subset of patients treated with definitive therapy will continue to have 
an elevated prostate specific antigen (PSA), suggestive of clinically occult metastatic disease 
at the time of diagnosis. Alternatively, a subset of these men will have local disease which was 
inadequately treated. Thus, in men presenting with an elevated PSA following initial local 
therapy, it is of critical importance to define the location and extent of disease in order to deliver 
salvage therapy to active sites of malignancy (i.e. local versus systemic therapy). Unfortunately, 
at the present time conventional imaging with bone scan, computed tomography (CT) and 
magnetic resonance imaging (MRI) are woefully inadequate to detect small volume sites of 
disease.8-10 This has left clinicians to base decisions regarding the timing and mode of salvage 
treatment on imperfect clinical parameters such as PSA kinetics, surgical margin status and 
other pathologic data.11,12   
 
An alternative to conventional imaging is positron emission tomography (PET) combined with 
CT (PET/CT). PET/CT is a highly sensitive imaging modality that allows for the visualization of 
small volume sites of disease following accumulation of various radiotracers. In the field of 
oncology, PET/CT is most commonly performed using 18F-labeled fluorodeoxyglucose (FDG). 
Unfortunately, studies employing FDG have demonstrated mixed results in the imaging 
prostate cancer.13 Based on these data, many in the field have abandoned FDG PET/CT for 
the study of novel radiotracers against prostate cancer specific targets. One such target which 
has received considerable attention is prostate specific membrane antigen (PSMA). PSMA is 
a type II transmembrane glycoprotein found in approximately 95% of prostate cancer 
specimens.14 An FDA approved 111In-labeled antibody agent, ProstaScint15,16 has been 
previously used for single-photon emission computed tomography (SPECT) imaging of PSMA. 
Unfortunately, ProstaScint has fallen short in clinical testing owning issues of to low tissue 
permeability and slow clearance from the blood pool. To improve upon ProstaScint imaging, a 
handful of small molecule PET radiotracers have been developed and shown great promise in 
preclinical and early human testing.15,16   
 
In this study, we aim to preliminarily investigate the diagnostic utility of 18F-DCFPyL, a novel 
low-molecular weight PSMA PET/CT imaging agent17, in men with an elevated PSA following 
local treatment with radical prostatectomy. At the time of writing this protocol, 18F-DCFPyL has 
been studied in 9 men with metastatic prostate cancer and has proven safe without any serious 
adverse events (Appendix A). Moreover, 18F-DCFPyL has proven to be a highly sensitive 
imaging agent, detecting >400% more putative sites of disease as compared to conventional 
imaging techniques (Appendix B). Thus, given the outstanding safety and diagnostic sensitivity 
of this imaging agent, we hypothesize that 18F-DCFPyL PET/CT will aid in the evaluation of 
men with otherwise clinically unapparent sites of disease and perhaps one day help direct 
salvage therapy in the setting of an elevated PSA following failed local therapy.    
 
 
4. ENDPOINTS 
 
 
Description of the number and location of putative sites of metastatic disease as 
determined by 18F-DCFPyL PET/CT 
 
 
Correlation of findings on 18F-DCFPyL PET/CT with those found on conventional 
imaging (bone scan and cross-sectional imaging) 


5 
 
 
 
 
 
Correlation of findings on 18F-DCFPyL PET/CT with tissue histology and PSMA 
expression of biopsied/resected pathology specimens 
 
 
Assessment of treatment response by 18F-DCFPyL PET/CT following 6 months of 
management per the treating physician 
 
 
Correlation of 18F-DCFPyL PET/CT findings with PSA levels and time to disease 
progression 
 
 
5. PATIENT SELECTION & ELIGIBILITY 
 
5.1. NUMBER OF PATIENTS 
 
This study aims to enroll 50 participants. 
 
 
5.2. INCLUSION CRITERIA 
 
1. Age ≥18 years  
 
2. History of adenocarcinoma of the prostate treated with radical prostatectomy 
 
3. Serum PSA level ≥0.2 ng/mL at least 45 days prior to study enrollment  
 
4. Completed staging evaluation with bone scan as well as CT or MRI of the 
abdomen and pelvis at least 45 days prior to study enrollment 
 
5.3. EXCLUSION CRITERIA 
 
1. History of other malignancy (with the exception of squamous cell or basal cell 
carcinoma of the skin) diagnosed within the last 3 years  
 
2. Intention to enroll in a blinded therapeutic clinical trial 
 
 
 
5.4. INCLUSION OF WOMEN AND MINORITIES 
 
Males of all races and ethnic groups are eligible for this study and encouraged to 
participate. Women are excluded by virtue of the pathology being studied.   
 
 
6. SUBJECT RECRUITMENT AND  INFORMED CONSENT 
 
Urologists at Johns Hopkins will be educated about the study including patient eligibility criteria. 
At the treating physician’s discretion, patients will in turn be educated about the study and their 
interest in participation assessed. Any patient who expresses interest in participating in the 
study will then either be directly introduced to the study team staff, who will be present on select 
days in the urology clinic, or provided with the contact information of the study coordinator. 
Alternatively, patients learning about the protocol on ClinicalTrials.gov may contact the study 
coordinator directly. In all cases, as much time as is needed to consider study participation will 
be allowed to possible participants; resulting in multiple phone calls, visits, emails, or other 
communication, as necessary. 


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The principal investigator or designated individual will discuss the study with interested 
patients. Patients will be provided with the Institutional Review Board (IRB) approved consent 
form for review and given sufficient time to consider participation in the study. Once a decision 
has been made to enter into the study, a signature will be obtained from the patient to confirm 
consent.  
 
Patients may voluntarily withdraw consent at any point following enrollment in the study. At the 
time of informed consent patients will be instructed that they may withdraw consent by 
contacting the principal investigator or study coordinator.  
 
 
7. RISKS & BENEFITS 
 
7.1. RISKS 
 
18F-DCPyL is a novel imaging agent, which to date, has been studied in only 9 men with 
advanced prostate cancer under IRB protocol NA_00092956. Despite this small number, 
the compound appears to be very well tolerated with no reported serious adverse related 
events.    
 
During the course of this study patients will be exposed to 3.18 rem (1.59 rem per PET/CT) 
of radiation. 
 
The risks related to both DCFPyL and radiation exposure will be explained to the patient 
during the informed consent process.  
 
 
7.2. BENEFITS 
 
By participating in this research study, patients and their physicians will have access to the 
results of the PET/CT scans which may be used to personalize an individual patient’s 
cancer treatment plan. 
 
 
8. STUDY PROCEDURES 
 
1.  Eligability screening and informed consent  
 
2. 18F-DCFPyL PET/CT scan performed within 45 days of latest PSA, bone scan and 
cross-sectional imaging  
 
3.  Assessment of adverse events via phone call at 1-3 days following PET/CT 
 
4.  Management per the treating physician including periodic PSA measurements and 
re-staging imaging as clinically indicated 
 
5. 
18F-DCFPyL PET/CT scan performed 6 months following the first PET/CT (window 
-1 to +2 months) 
 
6. Assessment of adverse events via phone call at 1-3 days following PET/CT 
 
 
7. Collection of PSA, imaging and treatment data generated as part of routine clinical 
care for up to three years following the second 18F-DCFPyL PET/CT 


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9. PROTOCOL FOR 18F-DCFPYL PET/CT 
 
1. Patient will fast for 4 to 6 hours prior to injection of 18F-DCFPyL 
 
2. An intravenous peripheral intravenous catheter will be placed (or an upper-extremity 
existing central line accessed) in order to inject the radiotracer 
 
3. Intravenous fluid (5% dextrose + 0.45% normal saline) will be delivered at a low flow 
rate during the duration of the study (maximum 2 litters) 
 
4. A bolus of less than or equal to 9 mCi (333 MBq) of 18F-DCPyL will be injected into the 
IV line by slow push 
 
5. At approximately 60 minutes after the administration of 18F-DCFPyL, IV fluids will be 
discontinued and the patient will be asked to void.  A whole-body CT and PET scan 
will then be acquired from the mid-thigh to the vertex of the skull. The PET/CT will be 
performed on a Discovery DRX PET/CT scanner (GE Healthcare) operating in 3-
dimensional emission acquisition mode.  Scans will include approximately 8 to 9 
fields-of-view, depending on patient height.  
 
6. Temporary IV access will be removed 
 
 
10. STUDY STATISTICS 
 
Descriptive statistics (i.e. proportions/percentages for categorical variables and medians with 
interquartile ranges for continuous variables) will be used to detail the study cohort and findings 
on18F-DCFPyL PET/CT. More specifically, we plan to report data individually and in aggregate 
for patient age, race/ethnicity, TNM stage, pathologic Gleason score, surgical margin status, 
prior cancer treatment and interval treatment following the first PET/CT scan. Additionally we 
will report the number and location of putative sites of disease detected on PET/CT for both 
time points. These putative sites will be correlated to findings on available bone scan and cross-
sectional imaging obtained during the course of routine clinical care and their rate of 
concordance reported with 95% confidence intervals. Similarly, we plan to correlate findings on 
PET/CT scan with the tissue histology and PSMA expression (as determined by 
immunohistochemistry) of pathology specimens collected in follow-up as part of routine clinical 
care. Finally, we plan to evaluate change in the number, size and SUVmax/SUVmean values of 
putative sites of disease following 6 months of therapy as prescribed by the treating physician. 
For this analysis, paired scans will analyzed with the McNemar's test for categorical variables 
and the Wilcoxon signed-rank test for continuous variables. As an additional secondary 
endpoint, PET/CT findings will be correlated with serial PSA values as well as time to disease 
progression. 
 
 
11. SAFETY MONITORING 
 
Patients will be contacted 1 to 3 days following each 18F-DCFPyL PET/CT via phone call by a 
designated study team member to assess for study related adverse events. Any patient 
experiencing an adverse event will be instructed to go to the nearest emergency room for 
evaluation by a physician. The outcome of this call with appropriate follow-up will be 
documented in the medical record as a phone note. All adverse events will be recorded using 
Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 and will be submitted 
to the IRB per policy 103.6b. 


8 
 
 
 
 
 
12. DATA HANDLING AND RECORD KEEPING 
 
Paper consent forms, enrollment check sheets and W9 forms will be kept in a study binder. 
This binder will be stored in a locked office available only to the study team. 
 
Electronic data will be housed in a secure password protected REDCap database 
maintained by the Data Informatics Services Core within the Johns Hopkins Biostatistics 
Center. Only the study coordinator and investigators will have access to this secure 
database. Of note, to maintain the protected healthy information of patients enrolled in this 
study, only the study Principal Investigator and coordinator will have the ability to export 
data containing identifying information from this master database. For the purposes of 
analysis, only de-identified data will be exported.  
 
 
13. DISCLOSURE OF DATA 
 
The results of each 18F-DCFPyL PET/CT will be made available to both patients and treating 
physicians. Because this is a novel diagnostic test, all will parties requesting scan data will 
be explicitly reminded as to the experimental nature of the results. Additionally, at the time 
of informed consent, it will be explained to patients that the results of these scans may 
prompt additional confirmatory imaging and/or invasive procedures that would not have 
otherwise been contemplated had the patient not participated in this study. 
 
 
14. PATIENT REMUNERATION 
 
Following successful completion of each 18F-DCFPyL PET/CT, patients will be compensated 
with $100 and a voucher for free parking.  
 
 
15. FUNDING 
 
The study will be supported by private philanthropic funds raised by the Johns Hopkins 
Department of Urology.  
 
 
16. REFERENCES 
 
1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015; 65(1): 5-
29. 
 
2. Li J, Djenaba JA, Soman A, Rim SH, Master VA. Recent trends in prostate cancer incidence 
by age, cancer stage, and grade, the United States, 2001-2007. Prostate Cancer. 2012; 
2012: 691380.  
 
3. Mahmood U, Levy LB, Nguyen PL, Lee AK, Kuban DA, Hoffman KE. Current clinical 
presentation and treatment of localized prostate cancer in the United States. J Urol. 2014; 
192(6): 1650-6. 
 
4. Heidenreich A1, Bastian PJ, Bellmunt J, et al. EAU guidelines on prostate cancer. part 1: 
screening, diagnosis, and local treatment with curative intent-update 2013. Eur Urol. 2014; 
65(1):124-37.  
 


9 
 
 
 
5. Boorjian SA, Thompson RH, Tollefson MK, et al. Long-term risk of clinical progression after 
biochemical recurrence following radical prostatectomy: the impact of time from surgery to 
recurrence. Eur Urol. 2011; 59(6): 893-9. 
 
6. Mullins JK, Feng Z, Trock BJ, Epstein JI, Walsh PC, Loeb S. The impact of anatomical 
radical retropubic prostatectomy on cancer control: the 30-year anniversary. J Urol. 2012; 
188(6): 2219-24. 
 
7. Boorjian SA, Eastham JA, Graefen M, et al. A critical analysis of the long-term impact of 
radical prostatectomy on cancer control and function outcomes. Eur Urol. 2012; 61(4): 664-
75.  
 
8. Kane CJ, Amling CL, Johnstone PA, et al. Limited value of bone scintigraphy and computed 
tomography in assessing biochemical failure after radical prostatectomy.  Urology. 2003; 
61(3): 607-11. 
 
9. Dotan ZA, Bianco FJ Jr, Rabbani F, et al. Pattern of prostate-specific antigen (PSA) failure 
dictates the probability of a positive bone scan in patients with an increasing PSA after 
radical prostatectomy. J Clin Oncol. 2005; 23(9): 1962-8. 
 
10. Beresford MJ, Gillatt D, Benson RJ, Ajithkumar T. A systematic review of the role of imaging 
before salvage radiotherapy for post-prostatectomy biochemical recurrence. Clin Oncol (R 
Coll Radiol). 2010; 22(1): 46-55.  
 
11. Punnen S, Cooperberg MR, D'Amico AV, et al. Management of biochemical recurrence 
after primary treatment of prostate cancer: a systematic review of the literature. Eur Urol. 
2013; 64(6): 905-15. 
 
12. Zaorsky NG, Raj GV, Trabulsi EJ, Lin J, Den RB. The dilemma of a rising prostate-specific 
antigen level after local therapy: what are our options? Semin Oncol. 2013; 40(3):322-36. 
 
13. Cho SY, Szabo Z. Molecular imaging of urogenital diseases. Semin Nucl Med. 2014; 44(2): 
93-109.  
 
14. Minner S, Wittmer C, Graefen M, et al. High level PSMA expression is associated with early 
PSA recurrence in surgically treated prostate cancer. Prostate. 2011; 71(3): 281-8.  
 
15. Mease RC. Radionuclide based imaging of prostate cancer. Curr Top Med Chem. 2010; 
10(16): 1600-16. 
 
16. Mease RC, Foss CA, Pomper MG. PET imaging in prostate cancer: focus on prostate-
specific membrane antigen. Curr Top Med Chem. 2013; 13(8): 951-62. 
 
17. Chen Y, Pullambhatla M, Foss CA, et al. 2-(3-{1-Carboxy-5-[(6-[18F]fluoro-pyridine-3-
carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid, [18F]DCFPyL, a PSMA-based PET 
imaging agent for prostate cancer. Clin Cancer Res. 2011; 17(24): 7645-53. 
 
 
 


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Appendix A. Safety of 18F-DCFPyL PET/CT in 9 Patients with Metastatic Prostate 
Cacncer1 
 
 
1Data current as of February 29, 2015 
 
2Adverse events included headache and epistaxis in the same patient and thrombocytopenia 
in a separate patient. All adverse events were grade 1 and categorized as unlikely to be 
related to radiotracer administration. 
 
 
Type of Event 
Number Encountered 
All Adverse Events 
3 (33.3%)2 
Life-Threatening Adverse Event or Life-
Threatening Suspected Adverse Reaction 
0 
Serious Adverse Event or Serious Suspected 
Adverse Reaction 
0 
Suspected Adverse Reaction 
0 
Unexpected Adverse Event or Unexpected 
Suspected Adverse Reaction 
0 


11 
 
 
 
Appendix B. 18F-DCFPyL PET/CT Imaging Data from 9 Patients with Metastatic Prostate Cancer1 
 
CECT = contrast-enhanced CT, BS = bone scan, CIM = conventional imaging modalities (CECT + BS) 
 
1Data current as of February 29, 2015 
 
Modality 
All lesions 
Bone lesions 
Lymph node lesions 
Prostate, Prostate bed, 
Peri-prostatic tissue, and 
Other soft tissue lesions 
Definite 
Equivocal 
Definite 
Equivocal 
Definite 
Equivocal 
Definite 
Equivocal 
18F-DCFPyL 
PET/CT 
138 
1 
73 
1 
56 
0 
9 
0 
CECT 
20 
11 
8 
9 
7 
0 
5 
2 
BS 
13 
5 
13 
5 
N/A 
N/A 
N/A 
N/A 
Combined CIM 
30 
15 
18 
13 
7 
0 
5 
2