Clinical trial NCT02687139
Conditions: Renal Cell Carcinoma Kidney Cancer
Sponsor: Johns Hopkins University
Start date: 2015-10-01; Completion date: 2019-04-01
Enrollment: 34 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
In this study the investigators aim to evaluate diagnostic utility of prostate-specific membrane antigen (PSMA)-targeted 18F-DCFPyL PET/CT in patients with renal cell carcinoma (RCC).

Detailed description:

Arms: arm 1: None
Interventions: intervention 1: 18F-DCFPyL intervention 2: PET/CT
Intervention descriptions: intervention 1: None intervention 2: Positron Emission Tomography - Computed Tomography (PET/CT)

Protocol documents:
Prot_SAP_000.pdf: 
 
Study Title:      Study of 18F-DCFPyL PET/CT in the Assessment of 
                                Patients with Renal Cell Carcinoma 
 
Principal Investigator: Mohamad E. Allaf, M.D. 
 
NCT number:   02687139 
 
 Protocol date:  February 26, 2017 
 
 
 


1 
 
Protocol Title:  
Study of 18F-DCFPyL PET/CT in the Assessment of 
Patients with Renal Cell Carcinoma 
 
 
Principal Investigator:  
Mohamad E. Allaf, M.D.1 
 
 
Research Nurses: 
Carolyn Chapman, B.A., R.N. 2 
 
Tanya O'Neal, B.S.N, R.N., M.S.N.2 
 
 
 
Study Coordinators:  
Akimosa Jeffrey-Kwanisai3 
 
Ghedem Solomon3 
 
Laura Webster1 
 
 
 
 
Regulatory Staff:  
Ting Wang, M.S.2 
 
Rehab A. AbdAllah, M.B. B.Ch.2 
 
Affiliations: 
1Depatment of Urology and The James Buchanan Brady 
Urological Institute 
 
2Department of Oncology, Sidney Kimmel 
Comprehensive Cancer Center 
 
3The Russell H. Morgan Department of Radiology and 
Radiological Science, Division of Nuclear Medicine 
 
 
 
Johns Hopkins University School of Medicine 
 
Baltimore, MD, USA 
 
 
eIRB2 ID:  
IRB00075596 
 
 
J Number:  
J15145 
 
 
IND Number: 
121064 
 
 
 
Version Date: 
February 26, 2017 
 
 


2 
 
1. STUDY SUMMARY 
 
PROTOCOL TITLE 
Study of 18F-DCFPyL PET/CT in the 
Assessment of Patients with Renal Cell 
Carcinoma 
IRB NUMBER 
IRB00075596 
J Number 
J15145 
IND NUMBER 
121064   
INVESTIGATIONAL AGENT 
18F-DCFPyL 
PATIENT POPULATION 
Patients with localized high-risk (T2-4N0M0) or 
metastatic (TanyN1M0 or TanyNanyM1) renal cell 
carcinoma 
SAMPLE SIZE 
N = 35 
OBJECTIVES 
 To investigate the sensitivity of 18F-DCFPyL 
PET/CT for detecting sites of disease in 
patients with localized high-risk (T2-4N0M0) 
or metastatic (TanyN1M0 or TanyNanyM1) 
renal cell carcinoma. 
 
 To correlate sites of radiotracer uptake on 
18F-DCFPyL PET/CT with conventional 
imaging findings. 
 
 To correlate sites of radiotracer uptake on 
18F-DCFPyL PET/CT with locations of 
disease recurrence/progression. 
 
 To correlate sites of radiotracer uptake on 
18F-DCFPyL PET/CT with the histology of 
biopsied or resected tissue specimens. 
 
 To correlate findings on 18F-DCFPyL 
PET/CT with duration of progression-free 
survival. 
 
 
 


3 
 
2. BACKGROUND & RATIONALE 
 
Renal cell carcinoma (RCC) is the third most common genitourinary malignancy with 
more than 60,000 new cases diagnosed each year in the United States alone [1]. In 
the context of metastatic RCC, definitive assessment of small lesions (i.e. <1 cm) as 
well as response to systemic therapy can be challenging with currently available 
anatomic imaging modalities such as contrast-enhanced computed tomography (CT) 
and magnetic resonance imaging (MRI) [2]. In many non-urologic malignancies, 
these difficult diagnostic tasks are often performed with the quantitative metabolic 
information available with 
18F-fluorodeoxyglucose (FDG) positron 
emission 
tomography (PET)/CT [3]. While 18F-FDG PET/CT can reliably identify sites of 
metastatic RCC [4], indeterminate lesions are still common and a role for monitoring 
treatment response has not been clearly established [5].    
 
One characteristic feature of RCC is that sites of disease are highly vascularized, 
raising the possibility that a PET radiotracer targeting the tumor neovasculature 
could reliably image metastatic lesions. One potential target for such a radiotracer is 
the cell surface protein, prostate-specific membrane antigen (PSMA), which, despite 
the specificity implied by its name, is highly expressed in the tumor neovasculature 
of a number of solid tumors including a variety of RCC subtypes [6, 7]. The potential 
utility of imaging of RCC with PSMA-targeted radiotracers was recently 
demonstrated in a small series of 5 patients with metastatic clear cell RCC imaged 
with the 18F-labeled low-molecular weight PSMA ligand 2-(3-{1-Carboxy-5-[(6-
[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic 
acid, 
more 
commonly known as 18F-DCFPyL [8]. In all five patients, sites of putative metastatic 
disease were readily identified by abnormal 18F-DCFPyL uptake, with more lesions 
detected on PET/CT than conventional imaging (18 vs. 28 lesions). These PET 
detected sites included lesions of the bone, brain, lymph nodes, soft tissue and 
abdominal viscera. 18F-DCFPyL uptake ranged from subtle to intense with maximum 
standardized uptake values (SUVmax) ranging from 1.6 to 19.3.  
 
In this pilot study we aim to expand upon the limited existing data on PSMA PET/CT 
of RCC by imaging a cohort of patients with kidney cancer over a range of disease 
stages (stage II-IV) and without restriction to the clear cell histologic type. These 
preliminary data may then serve to aid in hypothesis generation for the planning of 
future studies.   
 
 
3. OBJECTIVES 
 
 To investigate the sensitivity of 18F-DCFPyL PET/CT for detecting sites of 
disease in patients with localized high-risk (T2-4N0M0) or metastatic 
(TanyN1M0 or TanyNanyM1) renal cell carcinoma. 
 
 To correlate sites of radiotracer uptake on 18F-DCFPyL PET/CT with 
conventional imaging findings.  
 
 To correlate sites of radiotracer uptake on 18F-DCFPyL PET/CT with locations 
of disease recurrence/progression.  


4 
 
 To correlate sites of radiotracer uptake on 18F-DCFPyL PET/CT with the 
histology of biopsied or resected tissue specimens collected during the course 
of routine clinical care.  
 
 To correlate findings on 18F-DCFPyL PET/CT with duration of progression-
free survival. 
 
 
4. PATIENT SELECTION & ELIGIBILITY 
 
4.1. NUMBER OF PATIENTS 
 
During the course of this study we aim to enroll 35 patients  
 
 
4.2. INCLUSION CRITERIA 
 
1. Age ≥18 years  
 
2. Clinically diagnosed or histologically proven stage II-IV (T2-4N0M0, 
TanyN1Many, TanyNanyM1) renal cell carcinoma 
 
3. Completed staging evaluation with CT or MRI of the chest, abdomen and 
pelvis ≤90 days prior to study enrollment 
 
 
4.3. EXCLUSION CRITERIA 
 
1. History of other malignancy diagnosed within the last 3 years (with the 
exception of low risk prostate cancer [Gleason score 6, pretreatment PSA 
≤10, cT2a or pT2 if treated], DCIS of the breast, squamous cell carcinoma 
or basal cell carcinoma of the skin)  
 
2. Administered a radioisotope within 5 physical half-lives prior to study 
enrollment 
 
3. Pregnancy (as determined in accordance with the policies of the PET 
center) 
 
4. Intention to enroll in a blinded therapeutic clinical trial following PET/CT 
 
 
 
 
4.4. INCLUSION OF WOMEN AND MINORITIES 
 
Men and women of all races and ethnic groups are eligible for this study and 
encouraged to participate.  
 
 
 


5 
 
5. SUBJECT RECRUITMENT AND  INFORMED CONSENT 
 
Urologists and medical oncologists at Johns Hopkins will be educated about the 
study including patient eligibility criteria. At the treating physician’s discretion, 
patients will in turn be informed 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 
clinic days, or their contact information provided to the study coordinator. 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. 
 
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.  
 
 
6. RISKS & BENEFITS 
 
6.1. RISKS 
 
18F-DCPyL is a novel imaging agent, which to date, has been studied in <50 
patients at Johns Hopkins under existing IRB protocols (IRB00046315, 
IRB00062296, 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 1.59 rem of radiation. 
The risks related to both 18F-DCFPyL and radiation exposure will be explained to 
the patient during the informed consent process.  
 
 
6.2. BENEFITS 
 
There will be no direct medical benefit to participants participating in this study. 
Rather, their participating may help patients in the future by further our 
knowledge of RCC.  
 
 
 
 
 


6 
 
7. STUDY PROCEDURES 
 
1. Eligability screening  
 
2. Informed consent 
 
3. Completion of data collection sheet, KPS score, ECOG performance status 
and FKSI-19 questionaire  
 
4. 18F-DCFPyL PET/CT scan  
 
5.  Assessment of adverse events via phone call at 1-3 days following 
PET/CT 
 
6.  Treatment per the treating physician including imaging as clinically 
indicated 
 
7.  Collection of clinic notes, surgical reports, imaging test results/images, 
pathology reports and pathology/tissue specimens in the form of slides or 
paraffin blocks which are generated as part of routine clinical care for up to 
five years following study enrollment 
 
 
8. 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 
 
 
 
 


7 
 
9. STUDY STATISTICS 
 
Descriptive statistics (i.e. proportions/percentages for categorical and medians with 
interquartile ranges for continuous variables) will be used to describe the study 
cohort and findings on 18F-DCFPyL PET/CT scans. More specifically, data will be 
reported on patient age, race/ethnicity, TNM stage, histologic RCC subtype, 
Fuhrman grade, surgical margin status, sites/burden of disease, prior cancer 
treatment and interval treatment following PET/CT scan. Additionally we will report 
the number and location of putative sites of disease detected on PET/CT. These 
sites will be correlated to findings on available conventional imaging as well as with 
histology of biopsied/resected tissue specimens obtained during the course of 
routine clinical care. Lastly, we will explore the relationship of PET/CT findings with 
the location and pattern of recurrence/progression as well as duration of 
progression-free survival. For any analysis of progression-free survival, Kaplan-Meir 
estimates will be calculated and groups will be compared with the log-rank test. 
Given the exploratory nature of this study, we do not have any predefined analyses 
in mind. We do envision, however, comparing the progression-free survival of 
patients after dichotomization/grouping by a number of different imaging parameters 
such as number of sites of disease, location of disease sites and mean SUVmax 
values.   
 
 
10. SAFETY MONITORING 
 
Patients will be contacted 1 to 3 days following the 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. 
 
 
11. DATA HANDLING AND RECORD KEEPING 
 
Paper consent forms and enrollment check sheets will be kept in a study binder. 
This binder will be stored in a locked office available only to the study team. 
 
Electronic data including patient demographics, pathology results, imaging data 
and treatment details 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 health 
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.  
 
 
 
 


8 
 
12. DISCLOSURE OF DATA 
 
The results of 18F-DCFPyL PET/CT scans will be made available to both patients 
and treating physicians. Because this is a novel diagnostic test which is being 
studied under an IND, the following statement will appear in all radiology reports: 
 
18F-DCFPyL 
PET/CT 
is 
currently 
being 
studied 
under 
an 
Investigational New Drug application from the United States Food and 
Drug Administration. This scan is considered experimental and the 
results should be interpreted in this context. Any treatment decisions 
made based on the results of this study should include a discussion 
with the patient as to the investigational nature of the scan and the 
possibility of basing management decisions on falsely positive and/or 
negative findings. 
 
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. 
 
 
13. PATIENT REMUNERATION 
 
Patients will be provided with a voucher for free parking following successful 
completion of the PET/CT. 
 
 
14. FUNDING 
 
The study will be supported by private philanthropic funds raised by the Johns 
Hopkins Department of Urology.  
 
 
 
 


9 
 
15. REFERENCES 
 
1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015; 
65: 5-29. 
 
2. Brufau BP, Cerqueda CS, Villalba LB, Izquierdo RS, González BM, Molina CN. 
Metastatic renal cell carcinoma: radiologic findings and assessment of response 
to targeted therapy by using multidetector CT. Radiographics. 2013; 33: 1691-
1716. 
 
3. Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: 
evolving considerations for PET response criteria in solid tumors. J Nucl Med. 
2009; 50 Suppl 1: 122S-150S. 
 
4. Wang HY, Ding HJ, Chen JH, et al. Meta-analysis of the diagnostic performance 
of [18F]FDG-PET and PET/CT in renal cell carcinoma. Cancer Imaging. 2012; 
12: 464-474. 
 
5. Calderella C, Muoio B, Isgrò MA, Porfiri E, Treglia G, Giovanella L. The role of 
fluorine-18-fluorodeoxyglucose positron emission tomography in evaluating the 
response to tyrosine-kinase inhibitors in patients with metastatic primary renal 
cell carcinoma. Radiol Oncol. 2014; 48: 219-227. 
 
6. Chang SS, O’Keefe DS, Bacich DJ, Reuter VE, Heston WD, Gaudin PB. 
Prostate-specific 
membrane 
antigen 
is 
produced 
in 
tumor-associated 
neovasculature. Clin Cancer Res.  1999; 5: 2674-2681. 
 
7. Baccala A, Sercia L, Li J, Heston W, Zhou M. Expression of prostate-specific 
membrane antigen in tumor-associated neovasculature of renal neoplasms. 
Urology. 2007; 70: 385-390. 
 
8. Rowe SP, Gorin MA, Hammer HJ, et al. Imaging of metastatic clear cell renal cell 
carcinoma with PSMA-Targeted 18F-DCFPyL PET/CT. Ann Nucl Med. In press.  
 
 


10 
 
APPENDIX A. ELIGIBILITY CHECKLIST 
 
 
Name  
 
 
 
_____________________________ 
Date of Birth  
 
 
_____________________________ 
Medical Record Number 
 
_____________________________ 
Date Eligibility Screened 
 
_____________________________ 
Person Performing Screening 
_____________________________ 
 
Gender:              M                F 
 
Race/Ethnicity (check all that apply): 
 
American 
Indian or 
Alaskan 
Native 
Asian 
Native 
Hawaiian 
or Other 
Pacific 
Islander 
Black or 
African 
American
White 
Unknown
Other 
 
Non-
Hispanic 
 
 
 
 
 
 
 
Hispanic 
or Latino 
 
 
 
 
 
 
 
Unknown
 
 
 
 
 
 
 
 
 
PATIENT ELIGIBILITY 
Inclusion Criteria 
(Criteria should be answered YES for patient to be eligible.) 
YES 
NO 
1. 
Age ≥18 years 
 
 
2. 
Clinically diagnosed or histologically proven stage II-IV (T2-
4N0M0, TanyN1Many, TanyNanyM1) renal cell carcinoma 
 
 
3. 
Completed staging evaluation with CT or MRI of the chest, 
abdomen and pelvis ≤90 days prior to study enrollment 
 
 
 
Exclusion Criteria 
(Criteria should be answered NO for patient to be eligible.)
YES 
NO 
1. 
History of other malignancy diagnosed within the last 3 
years (with the exception of low risk prostate cancer 
[Gleason score 6, pretreatment PSA ≤10, cT2a or pT2 if 
treated], DCIS of the breast, squamous cell carcinoma or 
basal cell carcinoma of the skin)  
 
 
2. 
Administered a radioisotope within 5 physical half-lives prior 
to study enrollment 
 
 
3. 
Pregnancy (as determined in accordance with the policies of 
the PET center) 
 
 
4. 
Intention to enroll in a blinded therapeutic clinical trial 
following PET/CT