Clinical trial NCT03423082
Conditions: Cervical Cancer Uterine Cancer
Sponsor: Nghi Nguyen
Start date: 2018-12-11; Completion date: 2019-12-18
Enrollment: 1 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
18F Fluciclovine is a recently FDA- approved radiopharmaceutical for prostate cancer biochemical recurrence, which is only minimally eliminated by the kidneys and therefore the image interpretation is not affected by nonspecific urine activity in the ureters and bladder, which is advantageous for pelvic imaging. Recent literature suggests that Fluciclovine PET has diagnostic potential for a variety of solid tumors, thus, allowing new opportunities for noninvasive probing of glutamine metabolism and clinical use in patient management. Current literature indicates that amino acid transporters including that of glutamine are upregulated in endometrial and cervical cancer so that Fluciclovine PET may have clinical potentials. The hypothesis is that Fluciclovine PET provides better imaging properties and greater diagnostic confidence and accuracy than FDG PET does in pelvic malignancies.

Given the lack of current clinical data, a pilot study providing a direct comparison of Fluciclovine PET with FDG PET is warranted. The investigators seek to conduct a pilot study with 10 subjects to evaluate the clinical utility of Fluciclovine PET for staging of cervical cancer and endometrial cancer. This research will compare the diagnostic performance of the research Fluciclovine PET/MRI with the standard-of-care FDG PET/CT as an exploratory endpoint.

Detailed description:
Background:

Endometrial cancer arises from the inner lining of the uterus and is one of the most common malignancies in women, representing 3.6% of all new cancer cases in the US. It is estimated that there are more than 60,000 new cases of endometrial cancer and more than 10,000 people will die of this malignancy in 2016. It is most frequently diagnosed among women aged 55-64. Cervical cancer starts in the cervix, the lower part of the uterus. Its prevalence is lower compared with endometrial cancer thank to effective screening and early disease detection with the Pap smear. In 2016, it is estimated that there will be more than 12,000 new cases of cervical cancer and more than 4,000 patients will die of this disease in the US.

Positron Emission Tomography (PET) combined with Computed Tomography (CT) is an essential part of the workup for many malignancies. F-18 FDG PET/CT is currently the standard-of-care (SOC) PET/CT modality for staging and restaging of pelvic malignancies in women. But there are certain diagnostic limitations related to F-18 FDG because it is mainly eliminated by the kidneys and often interferes with the detection of cancer lesions, particularly in the abdominal and pelvic regions. On the other hand, the recently FDA approved F-18 Fluciclovine is only minimally eliminated by the kidneys and therefore the image interpretation is not affected by nonspecific urine activity in the ureters and bladder, which is advantageous for pelvic imaging. Recent literature suggests that Fluciclovine PET has diagnostic potential for a variety of solid tumors, thus, allowing new opportunities for noninvasive probing of glutamine metabolism and clinical use in patient management.

Current literature indicates that amino acid transporters including that of glutamine are upregulated in endometrial and cervical cancer so that Fluciclovine PET may have clinical potentials. The hypothesis is that Fluciclovine PET provides better imaging properties and greater diagnostic confidence and accuracy than FDG PET does in pelvic malignancies.

Given the lack of current clinical data, a pilot study providing a direct comparison of Fluciclovine PET with FDG PET is warranted.

Objective:

The investigators seek to conduct a pilot study to evaluate the clinical utility of Fluciclovine PET for staging of cervical cancer and endometrial cancer. This research will focus on pelvic imaging comparing the diagnostic performance of the research Fluciclovine PET/MRI with SOC FDG PET/CT as an exploratory endpoint. Dynamic PET imaging on a hybrid PET/MR scanner will provide valuable pharmacokinetic information that can be used to identify the optimal time window for the detection and characterization of the primary tumor and pelvic nodal disease. Additional abdominal imaging will allow for further correlation with FDG PET/CT in terms of nodal disease and distant metastasis detection. As previously demonstrated in prostate cancer, the Fluciclovine uptake can be heterogeneous which may have diagnostic and prognostic implications. Therefore, this pilot study will provide valuable information on potential Fluciclovine heterogeneity in cervical and uterine cancer. Textural heterogeneity of the primary will be compared between Fluciclovine and FDG PET. The initial experience gained with this pilot study will provide valuable insights into the pharmacokinetics and textural heterogeneity of Fluciclovine PET in cervical and uterine cancers, and presents the first data on the potential strengths and weaknesses of Fluciclovine PET/MR compared with FDG PET/CT.

1. The investigators hypothesize that Fluciclovine PET is non-inferior to FDG PET regarding detection of the primary tumor.
2. It is hypothesized that nodal disease staging is more accurate with Fluciclovine than with FDG PET because of the low level of nonspecific urinary bladder and ureter activity.
3. It is hypothesized that the dynamic uptake pattern of the primary lesion correlates with the tumor grading on histopathology.
4. It is hypothesized that textural heterogeneity is different between Fluciclovine and FDG PET.

Specific Aims:

* To study the pharmacokinetics of Fluciclovine PET in women with cervical and uterine cancers
* To characterize physiologic uptake pattern of the uterus and ovaries when these are not affected by tumor.
* To identify the optimal time window for the quantitative analysis of Fluciclovine primary and pelvic nodal disease
* To correlate the time-activity curve pattern of the primary lesion with histopathologic tumor grading
* To compare diagnostic performance of Fluciclovine PET and FDG PET
* To compare textural heterogeneity of the primary between Fluciclovine PET and FDG PET

Significance:

The initial experience gained with this pilot study will provide valuable insights into the pharmacokinetics, lesion detectability and textural heterogeneity of Fluciclovine PET in cervical cancer and uterine cancer. The study provides preliminary data on the potential strengths and weaknesses of Fluciclovine PET/MR compared with the SOC FDG PET/CT.

Fluciclovine PET may provide a significant improvement in the TNM staging compared with FDG PET as it is not affected by nonspecific urine activity in the ureters and bladder, which is a common diagnostic problem for FDG PET. By combining the excellent soft-tissue contrast of MRI with Fluciclovine PET, the hybrid PET/MR scanning could be a convenient and effective one-stop imaging procedure providing both pelvic TNM staging and whole-body M staging. Moreover, valuable prognostic information may be derived from Fluciclovine PET pharmacokinetics and heterogeneity assessment as well as multi-parametric PET/MR evaluation.

Arms: arm 1: Subjects with recently biopsy-proven malignancy of the cervix or uterus undergo an 18F fluciclovine PET scan on a hybrid PET/MRI scanner after they have completed a standard-of-care F-18 FDG PET/CT study.
Interventions: intervention 1: 18F fluciclovine intervention 2: 18F fluciclovine PET
Intervention descriptions: intervention 1: Each subject will receive one IV dose of 18F fluciclovine for PET scanning intervention 2: Each subject will undergo one 18F fluciclovine PET scan on a hybrid PET/MRI scanner

Protocol documents:
Prot_SAP_001.pdf: 
 
 
 
 
Axumin™ (fluciclovine F 18) Research Concept Proposal 
 
Name & contact 
information 
Principal Investigator 
Alternate Contact 
Nghi C. Nguyen, MD, PhD 
Assistant Professor of Radiology 
University of Pittsburgh 
UPMC Presbyterian 
200 Lothrop Street (at Meyran Ave) 
East Wing, 2nd Floor, Suite 200 
Pittsburgh, PA 15213 
Phone: 412-647-0104 
 
Institution 
 
Department of Radiology. University of Pittsburgh Medical Center (UPMC), 
Pittsburgh, Pennsylvania 
Study Title 
 
Pilot study to assess the clinical utility of F-18 fluciclovine PET for cervical and 
endometrial cancer compared with F-18 FDG PET 
Background/Rationale 
 
Endometrial cancer arises from the inner lining of the uterus and is one of the 
most common malignancies in women, representing 3.6% of all new cancer 
cases in the US. It is estimated that there are more than 60,000 new cases of 
endometrial cancer and more than 10,000 people will die of this malignancy in 
2016. It is most frequently diagnosed among women aged 55-64. Cervical 
cancer starts in the cervix, the lower part of the uterus. Its prevalence is lower 
compared with endometrial cancer thank to effective screening and early 
disease detection with the Pap smear. In 2016, it is estimated that there will be 
more than 12,000 new cases of cervical cancer and more than 4,000 patients 
will die of this disease in the US. 
Positron Emission Tomography (PET) combined with Computed Tomography 
(CT) is an essential part of workup for many malignancies. F-18 FDG PET/CT is 
being used clinically in the evaluation and management of pelvic malignancies 
in women. But there are certain diagnostic limitations related to F-18 FDG 
because it is mainly eliminated by the kidneys and often interferes with the 
detection of cancer lesion. On the other hand, the recently FDA approved F-18 
fluciclovine is not be eliminated by the kidneys and therefore the image 
interpretation is not affected by nonspecific urine activity in the ureters and 
bladder, which is advantageous for pelvic imaging. Recent literature suggests 
that F-18 fluciclovine has diagnostic potential for a variety of solid tumors, thus, 
allowing new opportunities for noninvasive probing of glutamine metabolism 
and for clinical use in patient management. 
Current literature indicates that amino acid transporters including that of 
glutamine are upregulated in endometrial and cervical cancer, so F-18 
fluciclovine PET may have clinical potential. The hypothesis is that F-18 
fluciclovine PET provides better imaging properties and greater diagnostic 
confidence and accuracy than F-18 FDG PET in pelvic malignancies. Given the 
lack of current clinical data, a pilot study providing a direct comparison of F-18 
Title: Pilot study to assess the clinical utility of F-18 fluciclovine PET for cervical and endometrial cancer compared with F-18 FDG PET
NCT03423082
Date: 10/19/2016


 
 
 
 
fluciclovine PET with FDG PET is warranted.  
(References: Cancer Res. 2014 Oct 15;74(20):5832-45. doi: 10.1158/0008-5472; J 
Biol Chem. 2016 Jun 17;291(25):13194-205. doi: 10.1074/jbc.M115.700534; 
Hum Pathol. 2011 Nov;42(11):1660-6. doi: 10.1016/j.humpath.2011.01.013)  
Study Objective(s) 
 
We seek to conduct a pilot study to evaluate the clinical utility of F-18 
fluciclovine for staging of cervical cancer and endometrial cancer. Our research 
will focus on the comparison of F-18 fluciclovine PET/MRI with the standard of 
care F-18 FDG PET/CT. Ten adult women with biopsy-proven endometrial cancer 
or cervical cancer scheduled for standard of care MRI of the pelvis for disease 
staging will be invited to participate in this research. Their clinical pelvic MRI 
scan will be performed on a PET/MR scanner (Siemens Biograph mMR) and 
combined with the research F-18 fluciclovine PET scan of the pelvis, with both 
MR and PET images acquired simultaneously. In addition, a whole-body PET/MR 
scan will be acquired for research only. The simultaneous PET/MR image 
acquisition is expected to provide significant improvement the TNM staging by 
combining the excellent soft-tissue contrast of MRI with F-18 fluciclovine PET, 
which is not affected by nonspecific urine activity in the ureters and bladder. 
The initial experience gained with this pilot study will provide valuable insights 
into the potential strengths and weaknesses of F-18 fluciclovine. The 
preliminary data will be used for sample size estimates for a R01 NIH grant 
application, which will validate the diagnostic accuracy as well as added value of 
F-18 fluciclovine PET compared with FDG PET/CT. In brief, the success of this 
pilot study will have significant implication for adopting F-18 fluciclovine PET for 
pelvic imaging in women. 
Study Design 
(inclusion/exclusion 
criteria  – patient 
population) 
 
Inclusion criteria: Adult females with newly diagnosed endometrial and cervical 
cancer for whom an FDG PET/CT scan and a pelvic MR scan are being 
considered for disease staging. 
Exclusion criteria: Patients < 18 years; patients without biopsy proven 
malignancy of the endometrium or cervix; only FDG PET/CT scan or pelvic MR 
scan is being considered for standard of care imaging. 
 
An integrated PET/MR scanner which is operational at UPMC Presbyterian since 
Fall 2012 will be used for this research. Two PET scans will be performed – a 
regional scan of the pelvis in conjunction with the standard of care pelvic MRI 
with IV contrast and an additional whole-body scan PET/MR scan for research 
only. The total scan time on the PET/MR scanner is 30-45 minutes. The PET/MR 
data will be then correlated with the standard of care FDG PET/CT data, 
acquired within 2 weeks of the PET/MR scan. 
Sample size and duration 
of follow-up  
There have been no prior reports on the use of F-18 fluciclovine PET; thus, a 
sample size of 10 subjects would be sufficient for preliminary data collection.  
Planned analyses 
Research F-18 fluciclovine PET images and standard of care FDG PET images will 
be evaluated by two readers for image quality, lesion conspicuity and diagnostic 
confidence using visual scores. Semi-quantitative parameters of maximum 
lesion standardized-uptake-value (SUV) and background mean SUV will be 
obtained. Nonparametric statistical analyses will be used to compare the visual 
scores and SUV values between the two PET scans.  


 
 
 
 
Timeframe for study start-
up & duration of study 
It is estimated that approximately 50 patients per year undergo FDG PET/CT and 
pelvic MR scans for disease staging at our referral center (Magee-Women’s 
Hospital of UPMC). Clinical PET/MR workflows for tumor imaging including the 
pelvis are in place, and technical staff is trained to perform clinical PET/MR 
scans. Close research collaborations exist between Radiology and Radiation 
Oncology at Magee-Women’s Hospital from where patients will be referred for 
this research. It takes about 3 months to get the IRB approved. Estimated start-
up time is 5 months; the duration for the study is 12 months.  
Support requested 
 
I am requesting free supply for the 10 F-18 fluciclovine doses and 20% salary 
support for a research coordinator for this 12-month project. The standard of 
care pelvic MRI will be billed to the patients’ health insurance.  
Other source(s) of funding The Department of Radiology would fund the scanner time incurred by the 
additional whole-body PET/MR scan (20-30 minutes). 
 
Date completed: October 19, 2016 
 
Please complete all relevant fields and email to Karen Linder, PhD, Sr Manager, Clinical Science and Medical  
Affairs. 
 
 
 
 
 
 
 
 
 
 
Contact Information: k.linder@blueearthdx.com 
 
 
O: +1-609-751-0587 
M: +1-609-608-6455