18F-DCFPyL PET/CT in Hepatocellular Carcinoma

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ClinicalTrials.gov Identifier: NCT05009979

Recruitment Status : Recruiting

First Posted : August 18, 2021

Last Update Posted : May 8, 2024

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Sponsor:

Information provided by (Responsible Party):

National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Study Description

Brief Summary:

Background:

A radiotracer (or tracer) is a radioactive substance. It is used in Positron Emission Tomography (PET) imaging to help see specific sites in the body. Researchers want to learn if a new tracer can help them better identify hepatocellular cancer (HCC) in people.

Objective:

To learn if a radiotracer called 18F-DCFPyL can identify sites of HCC better than current standard imaging.

Eligibility:

Adults aged 18 years and older who may have HCC based on previous standard imaging.

Design:

Participants will be screened with a medical history, physical exam, and blood tests. They will have a computed tomography (CT) and/or magnetic resonance imaging (MRI) scan.

Participants will have a whole-body PET/CT scan. The PET and CT scanners use x-rays to make pictures of the inside of the body. The PET uses a tracer to help make the pictures. Participants will get an intravenous (IV) injection of 18F-DCFPyL 1 hour before the scan.

Within two weeks, participants will have a 18F-FDG PET/CT scan. 18F-FDG is a commonly used tracer. They will get 18F-FDG via IV 1 hour before the scan.

Participants will have a CT/MRI within 2 months of the first 18F-DCFPyL PET/CT.

Participants will have standard treatment for their cancer. During treatment, they will have a tumor biopsy. If the biopsy shows they do not have HCC, they will be removed from the study.

For participants who have HCC and their cancer was identified in the 18F-DCFPyL PET/CT, they will have a second 18F-DCFPyL PET/CT and 18F-FDG PET/CT.

Participants will have follow-up visits every 3 months for 2 years. Then they will have yearly visits for 3 years.

Condition or disease	Intervention/treatment	Phase
Hepatocellular Carcinoma	Drug: F18-FDG Device: MRI Device: CT Drug: F18-DCFPyL	Phase 2

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Detailed Description:

Background:

Prostate specific membrane antigen is overexpressed in high-grade tumors, and increases when de-differentiation, metastatic or hormone-refractory disease occur, making the expression level a prognostic factor for disease outcome.

It has been shown that PSMA can be expressed not only on prostate cancer cells, but also on cell lines of other malignancies, as well as tumor endothelium.

A recent publication reported that nearly 95% of hepatocellular carcinoma (HCC) stained positive for PSMA in the tumor vasculature. Research suggests that the process of endothelial cell recruitment to HCC occurs early and throughout the process of hepatic tumorigenesis, making an endothelial cell tracer an ideal marker to detect early disease.

18F-DCFPyL, a second generation PSMA PET agent, binds with high affinity to PSMA yet clears rapidly from the blood pool and thus, whole-body PET imaging with this agent, may provide a new tool in staging high risk cancers and detecting recurrent disease.

We propose to expand our clinical work using 18F-DCFPyL, and evaluate its usefulness for detecting sites of hepatocellular carcinoma.

Objective:

To assess the ability of 18F-DCFPyL PET/CT imaging to detect sites of hepatocellular carcinoma

Eligibility:

Participants >= 18 years old

High radiological suspicion of hepatocellular carcinoma (HCC) with at least one measurable lesion on standard imaging modality (CT and/or MRI)

Eastern Cooperative Oncology Group (ECOG) Performance score of 0 to 2

Design:

This is a multi-site imaging study enrolling participants with suspected hepatocellular carcinoma. The accrual ceiling is set to 50 participants.

All participants will undergo a baseline 18F-DCFPyL PET/CT scan. A standard of care CT and/or MRI will be performed within 2 months of the 18F-DCFPyL PET/CT. Participants will be also scanned with an 18F-FDG PET/CT imaging within approximately 2 weeks of the 18F-DCFPyL PET/CT imaging.

Participants will be scheduled to undergo a biopsy prior to or during standard of care local treatment for HCC (e.g., resection, radiofrequency ablation, microwave ablation, transarterial embolization (TAE), stereotactic body radiotherapy (SBRT)).

Participants with a baseline positive 18F-DCFPyL-PET/CT imaging (i.e. with the presence of DCFPyL-avid tumor/s) and biopsy confirming HCC diagnosis will undergo a post-treatment 18F-DCFPyL PET/CT imaging during the first routine follow-up period, typically within 16 weeks. Subjects with negative tumor uptake at baseline 18F-DCFPyL-PET/CT will not be re-scanned post-treatment but will remain in follow-up.

Participants with a positive HCC biopsy will be followed for 5 years to assess progression free survival.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	50 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Diagnostic
Official Title:	18F-DCFPyL PET/CT in Hepatocellular Carcinoma
Actual Study Start Date :	January 18, 2023
Estimated Primary Completion Date :	June 1, 2025
Estimated Study Completion Date :	December 1, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1/Baseline and Post-treatment Imaging 18F-DCFPyL PET/CT imaging, CT and/or MRI and standard of care local ablative treatment	Drug: F18-FDG Within approximately 2 weeks of each 18F-DCFPyL PET/CT scan, participants will be scanned with a 18F-FDG PET/CT imaging at the NIH Clinical Center using standard procedures. The 18F-FDG PET/CT imaging performed will allow the localization of viable tumor sites and characterize their FDG metabolism for comparison with 18F-DCFPyL imaging. The 18F-FDG PET/CT imaging will consist of an 18F-FDG injection and PET/CT imaging performed approximately 1 hour post 18F-FDG injection. A corresponding low dose CT scan for attenuation correction and co-registration purposes will be performed prior to the PET image. Device: MRI A standard of care CT and/or MRI will be performed within 2 months of each 18F-DCFPyL PET/CT. Device: CT A standard of care CT and/or MRI will be performed within 2 months of each 18F-DCFPyL PET/CT. Drug: F18-DCFPyL Each subject will receive a single IV dose of 18F-DCFPyL by bolus injection at a rate of approximately 1 ml/3-5 sec. The maximum amount of injected active drug will be less than 4.02 microgram. The target administered activity will be 9 mCi. The 18F-DCFPyL PET/CT imaging will consist of the 18F-DCFPyL injection, followed by a approximately 45 min dynamic CT imaging of a single bed position (including the liver lesion), and a static whole-body PET/CT imaging (top of head to mid-thighs) performed at 1 hour (+/- 10 minutes) post 18F-DCFPyL injection. Only a single injection of 18F-DCFPyL is required. The initial 45 minutes dynamic regional scan will be used to determine the kinetics of 18F-DCFPyL within the tumor as compared with normal liver and other background.

Arm

Intervention/treatment

Experimental: 1/Baseline and Post-treatment Imaging

18F-DCFPyL PET/CT imaging, CT and/or MRI and standard of care local ablative treatment

Drug: F18-FDG

Within approximately 2 weeks of each 18F-DCFPyL PET/CT scan, participants will be scanned with a 18F-FDG PET/CT imaging at the NIH Clinical Center using standard procedures. The 18F-FDG PET/CT imaging performed will allow the localization of viable tumor sites and characterize their FDG metabolism for comparison with 18F-DCFPyL imaging. The 18F-FDG PET/CT imaging will consist of an 18F-FDG injection and PET/CT imaging performed approximately 1 hour post 18F-FDG injection. A corresponding low dose CT scan for attenuation correction and co-registration purposes will be performed prior to the PET image.

Device: MRI

A standard of care CT and/or MRI will be performed within 2 months of each 18F-DCFPyL PET/CT.

Device: CT

A standard of care CT and/or MRI will be performed within 2 months of each 18F-DCFPyL PET/CT.

Drug: F18-DCFPyL

Each subject will receive a single IV dose of 18F-DCFPyL by bolus injection at a rate of approximately 1 ml/3-5 sec. The maximum amount of injected active drug will be less than 4.02 microgram. The target administered activity will be 9 mCi. The 18F-DCFPyL PET/CT imaging will consist of the 18F-DCFPyL injection, followed by a approximately 45 min dynamic CT imaging of a single bed position (including the liver lesion), and a static whole-body PET/CT imaging (top of head to mid-thighs) performed at 1 hour (+/- 10 minutes) post 18F-DCFPyL injection. Only a single injection of 18F-DCFPyL is required. The initial 45 minutes dynamic regional scan will be used to determine the kinetics of 18F-DCFPyL within the tumor as compared with normal liver and other background.

Outcome Measures

Primary Outcome Measures :

Positive predictive value [ Time Frame: Baseline, post ablation, disease progression ]
The point estimates and 95% confidence intervals of the positive predictive value of 18F-DCFPyL PET/CT will be reported in which the confidence limits are the 2.5th and 97.5th percentile of the 2000 bootstrap samples obtained by random sample without replacement at the participant level to account for inter-lesion correlation.

Secondary Outcome Measures :

Lesion level sensitivity, specificity and positive predictive value [ Time Frame: Baseline, post ablation, disease progression ]
The lesion level sensitivity, specificity and positive predictive value of 18F-DCFPyL PET/CT and CT/MRI will be calculated and compared. The confidence interval for each estimate will be obtained from the bootstrap samples and the difference in the estimates between the imaging modalities will be compared by the Wald test with the standard error calculated from the bootstrap samples.
Change in 18F-DCFPyL PET/CT uptake between pre- and post-treatment [ Time Frame: Pre- and post-treatment HCC treatment ]
change in 18F-DCFPyL PET/CT uptake between pre- and post-treatment will be compared by paired Wilcoxon test.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

INCLUSION CRITERIA:
High radiological suspicion of hepatocellular carcinoma (LR4 or LR5 based on the most current version of LI-RADS) with at least one measurable lesion on standard imaging modality (CT and/or MRI).
Eligible for local therapies (included but not limited to surgical resection, stereotactic radiation therapy, transarterial chem/radio/bland embolization, microwave ablation, radiofrequency ablation).
Ability to take oral medication and be willing to adhere to the study intervention regimen.
Age >=18 years.
ECOG performance status <=2.
Known human immunodeficiency virus (HIV)-infected individuals must be on effective anti-retroviral therapy with undetectable viral load within 6 months.
Known chronic hepatitis B virus (HBV) infected individuals, must be on suppressive therapy with undetectable viral load.
Individuals with a history of hepatitis C virus (HCV) infection must have been treated and cured.
The effects of 18F-DCFPyL (study drug) on the developing human fetus are unknown. For this reason and because this agent as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for 2 months after each study PET/CT imaging. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
Ability of subject to understand and the willingness to sign a written informed consent document

EXCLUSION CRITERIA:

History of allergic reactions attributed to compounds of similar chemical or biologic composition to 18F-DCFPyL or other agents used in study.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Subjects with severe claustrophobia unresponsive to oral anxiolytics.
Other medical conditions deemed by the principal investigator (or associates) to make the subject unsafe/ineligible for protocol procedures.
Subjects weighing > 350 lbs (weight limit for scanner table), or unable to fit within the imaging gantry
Serum creatinine > 2 times the upper limit of normal
Pregnant women are excluded from this study because 18F-DCFPyL is an agent with the potential for teratogenic or abortifacient effects. as well as other agents used in this trial are known to be teratogenic.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05009979

Contacts

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Contact: Joy Zou, R.N.	(240) 760-6153	joy.zou@nih.gov
Contact: Freddy E Escorcia, M.D.	(240) 858-3062	freddy.escorcia@nih.gov

Locations

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United States, District of Columbia
Washington DC VA medical Center	Withdrawn
Washington, District of Columbia, United States, 20422
United States, Maryland
National Institutes of Health Clinical Center	Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

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Principal Investigator:	Freddy E Escorcia, M.D.	National Cancer Institute (NCI)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page This link exits the ClinicalTrials.gov site

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Mena E, Shih J, Chung JY, Jones J, Rabiee A, Monge C, Turkbey B, Lindenberg L, Salerno KE, Kassin M, Wood B, Hernandez J, Maass-Moreno R, Saboury B, Jakhete N, Molitoris JK, Unger KR, Choyke PL, Escorcia FE. Functional Imaging of Liver Cancer (FLIC): Study protocol of a phase 2 trial of 18F-DCFPyL PET/CT imaging for patients with hepatocellular carcinoma. PLoS One. 2022 Nov 11;17(11):e0277407. doi: 10.1371/journal.pone.0277407. eCollection 2022.

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Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT05009979
Other Study ID Numbers:	10000080 000080-C
First Posted:	August 18, 2021 Key Record Dates
Last Update Posted:	May 8, 2024
Last Verified:	May 6, 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes
Plan Description:	.All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.
Supporting Materials:	Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF)
Time Frame:	Clinical data available during the study and indefinitely.@@@@@@Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
Access Criteria:	Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. @@@@@@Genomic data are made available via dbGaP through requests to the data custodians.

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Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):


Imaging Liver Cancer Radiotracer PSMA

Additional relevant MeSH terms:

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Carcinoma Carcinoma, Hepatocellular Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Adenocarcinoma Liver Neoplasms	Digestive System Neoplasms Neoplasms by Site Digestive System Diseases Liver Diseases Fluorodeoxyglucose F18 Radiopharmaceuticals Molecular Mechanisms of Pharmacological Action

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