Pilot Study to Assess the Potential Clinical Utility of 18F Fluciclovine PET for Cervical and Endometrial Cancer.

• Sponsor: Nghi Nguyen (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03423082
• Collaborator: Blue Earth Diagnostics (Industry)
• Enrollment: 1
• Location: 1
• Arm: 1
• Actual Duration (Months): 12.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cervical Cancer; Uterine Cancer	Drug: 18F fluciclovine; Device: 18F fluciclovine PET	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Pilot Study to Assess the Potential Clinical Utility of 18F Fluciclovine PET for Cervical and Endometrial Cancer Compared With 18F FDG PET
• Actual Study Start Date: Dec 11, 2018
• Actual Primary Completion Date: Dec 18, 2019
• Actual Study Completion Date: Dec 18, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 18F fluciclovine PET scan 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.	Drug: 18F fluciclovine; Each subject will receive one IV dose of 18F fluciclovine for PET scanning; Other Names: Axumin ; Device: 18F fluciclovine PET; Each subject will undergo one 18F fluciclovine PET scan on a hybrid PET/MRI scanner

Outcome Measures

Primary Outcome Measures

1. Lesion Metabolic Avidity [Two weeks]

   Metabolic parameter of maximum standard-uptake-value (SUV) will be compared between research Fluciclovine PET and standard-of-care FDG PET to determine lesion metabolic avidity

Secondary Outcome Measures

1. Optimal Imaging Window [One hour]

   The optimal time window for tumor detection (primary, nodal metastasis) relative to physiologic and benign structures will be determined based on time-activity curves of the Fluciclovine PET scan.

2. Fluciclovine PET Time-activity Curve Correlation With Histopathologic Tumor Grading [One hour]

   The Fluciclovine time-activity curve of the primary tumor (time to peak, uptake intensity, and slope of washout) will be correlated with histopathologic tumor grading.

3. Textural Tumor Heterogeneity [Two weeks]

   Parameters of textural tumor heterogeneity will be compared between Fluciclovine PET and FDG PET, using the open-access LIFEx software. The software allows for an automatic evaluation of more than 50 parameters for textural analyses and shows the result of the best parameters for tumor heterogeneity; however, no specific marker or measure of heterogeneity is be predefined in this process.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Female

• 18 years and older

• Biopsy-proved cervical cancer or endometrial cancer within three months of study enrollment

• Standard-of-care (SOC) FDG PET/CT exam performed within 30 days of study enrollment

Exclusion Criteria:

• Female < 18 years old

• No history of cervical cancer or endometrial cancer

• Primary biopsy > 3 months of study enrollment

• Systemic therapy or radiation therapy initiated

• SOC FDG PET/CT exam performed > 30 days of study enrollment

• Therapeutic procedures (chemotherapy, radiation therapy) have been initiated

• Pregnancy or lactation

• Claustrophobia or inability to tolerate the imaging procedure on the PET/MR scanner

• Individual is not willing to give informed consent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UPMC Presbyterian - MR Research Center	Pittsburgh	Pennsylvania	United States	15213

Sponsors and Collaborators

• Nghi Nguyen
• Blue Earth Diagnostics

Investigators

• Principal Investigator: Nghi C Nguyen, MD, PhD, Assistant Professor of Radiology

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 19, 2016

More Information

Publications

None provided.

• Responsible Party: Nghi Nguyen, Associate Professor, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT03423082
• Other Study ID Numbers: PRO17120310
• First Posted: Feb 6, 2018
• Last Update Posted: Oct 28, 2020
• Last Verified: Oct 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Endometrial Neoplasms; Uterine Neoplasms

Study Results

Participant Flow

Arm/Group Title	18F Fluciclovine PET Scan
Arm/Group Description	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. 18F fluciclovine: Each subject will receive one IV dose of 18F fluciclovine for PET scanning 18F fluciclovine PET: Each subject will undergo one 18F fluciclovine PET scan on a hybrid PET/MRI scanner
Period Title: Overall Study
STARTED	1
COMPLETED	1
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	18F Fluciclovine PET Scan
Arm/Group Description	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. 18F fluciclovine: Each subject will receive one IV dose of 18F fluciclovine for PET scanning 18F fluciclovine PET: Each subject will undergo one 18F fluciclovine PET scan on a hybrid PET/MRI scanner
Overall Participants	1
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	1 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	1 100%
Male	0 0%
Race and Ethnicity Not Collected (Count of Participants)

Outcome Measures

1. Primary Outcome

Title	Lesion Metabolic Avidity
Description	Metabolic parameter of maximum standard-uptake-value (SUV) will be compared between research Fluciclovine PET and standard-of-care FDG PET to determine lesion metabolic avidity
Time Frame	Two weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	18F Fluciclovine PET Scan
Arm/Group Description	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. 18F fluciclovine: Each subject will receive one IV dose of 18F fluciclovine for PET scanning 18F fluciclovine PET: Each subject will undergo one 18F fluciclovine PET scan on a hybrid PET/MRI scanner
Measure Participants	1
SUV of standard-of-care FDG	21.5
SUV of research Fluciclovine	6.5

2. Secondary Outcome

Title	Optimal Imaging Window
Description	The optimal time window for tumor detection (primary, nodal metastasis) relative to physiologic and benign structures will be determined based on time-activity curves of the Fluciclovine PET scan.
Time Frame	One hour

Outcome Measure Data

Analysis Population Description

Only one subject measured, so unable to determine optimal time window

Arm/Group Title	18F Fluciclovine PET Scan
Arm/Group Description	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. 18F fluciclovine: Each subject will receive one IV dose of 18F fluciclovine for PET scanning 18F fluciclovine PET: Each subject will undergo one 18F fluciclovine PET scan on a hybrid PET/MRI scanner
Measure Participants	0

3. Secondary Outcome

Title	Fluciclovine PET Time-activity Curve Correlation With Histopathologic Tumor Grading
Description	The Fluciclovine time-activity curve of the primary tumor (time to peak, uptake intensity, and slope of washout) will be correlated with histopathologic tumor grading.
Time Frame	One hour

Outcome Measure Data

Analysis Population Description

Only one subject measured, so unable to determine correlation of time-activity-curve with histopathology.

Arm/Group Title	18F Fluciclovine PET Scan
Arm/Group Description	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. 18F fluciclovine: Each subject will receive one IV dose of 18F fluciclovine for PET scanning 18F fluciclovine PET: Each subject will undergo one 18F fluciclovine PET scan on a hybrid PET/MRI scanner
Measure Participants	0

4. Secondary Outcome

Title	Textural Tumor Heterogeneity
Description	Parameters of textural tumor heterogeneity will be compared between Fluciclovine PET and FDG PET, using the open-access LIFEx software. The software allows for an automatic evaluation of more than 50 parameters for textural analyses and shows the result of the best parameters for tumor heterogeneity; however, no specific marker or measure of heterogeneity is be predefined in this process.
Time Frame	Two weeks

Outcome Measure Data

Analysis Population Description

Only one subject measured, so parameter output of software program would not be appropriate.

Arm/Group Title	18F Fluciclovine PET Scan
Arm/Group Description	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. 18F fluciclovine: Each subject will receive one IV dose of 18F fluciclovine for PET scanning 18F fluciclovine PET: Each subject will undergo one 18F fluciclovine PET scan on a hybrid PET/MRI scanner
Measure Participants	0

Adverse Events

Time Frame	One hour.
Arm/Group Title	18F Fluciclovine PET Scan
Arm/Group Description	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. 18F fluciclovine: Each subject will receive one IV dose of 18F fluciclovine for PET scanning 18F fluciclovine PET: Each subject will undergo one 18F fluciclovine PET scan on a hybrid PET/MRI scanner
All Cause Mortality
	18F Fluciclovine PET Scan
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Serious Adverse Events
	18F Fluciclovine PET Scan
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Other (Not Including Serious) Adverse Events
	18F Fluciclovine PET Scan
	Affected / at Risk (%)	# Events
Total	0/1 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.