18F-DCFPyL PET/CT in Hepatocellular Carcinoma

Phase 2

Terminated

Conditions: Hepatocellular Carcinoma

Interventions: Drug: F18-FDG
Device: MRI
Device: CT
Drug: F18-DCFPyL
Procedure: Tumor biopsy

Registration Number: NCT05009979

Lead Sponsor: National Cancer Institute (NCI)

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 piflufolastat F-18 (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 positron emission tomography (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 Fludeoxyglucose F 18 (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/magnetic resonance imaging (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.

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 prostate-specific membrane antigen (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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 8

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm 1, Cohort 1 Baseline and Post-treatment Imaging with Piflufolastat F-18 (18F-DCFPyL)	F18-FDG	Piflufolastat F-18 (18F-DCFPyL) positron emission tomography computed tomography (PET/CT) imaging, CT and/or magnetic resonance imaging (MRI) and standard of care local ablative treatment
Arm 1, Cohort 1 Baseline and Post-treatment Imaging with Piflufolastat F-18 (18F-DCFPyL)	MRI	Piflufolastat F-18 (18F-DCFPyL) positron emission tomography computed tomography (PET/CT) imaging, CT and/or magnetic resonance imaging (MRI) and standard of care local ablative treatment
Arm 1, Cohort 1 Baseline and Post-treatment Imaging with Piflufolastat F-18 (18F-DCFPyL)	CT	Piflufolastat F-18 (18F-DCFPyL) positron emission tomography computed tomography (PET/CT) imaging, CT and/or magnetic resonance imaging (MRI) and standard of care local ablative treatment
Arm 1, Cohort 1 Baseline and Post-treatment Imaging with Piflufolastat F-18 (18F-DCFPyL)	F18-DCFPyL	Piflufolastat F-18 (18F-DCFPyL) positron emission tomography computed tomography (PET/CT) imaging, CT and/or magnetic resonance imaging (MRI) and standard of care local ablative treatment
Arm 1, Cohort 1 Baseline and Post-treatment Imaging with Piflufolastat F-18 (18F-DCFPyL)	Tumor biopsy	Piflufolastat F-18 (18F-DCFPyL) positron emission tomography computed tomography (PET/CT) imaging, CT and/or magnetic resonance imaging (MRI) and standard of care local ablative treatment

Primary Outcome Measures

Name	Time	Method
Positive Predictive Value (PPV) Defined as the Proportion of Histopathology Positive Lesions as Measured by the Maximum Standardized Uptake (SUVmax) Value	Baseline, post ablation, and disease progression, an average of 3.87 months	Positive predictive value is defined as the proportion of histopathologically positive lesions. Positron emission tomography (PET) positivity was measured by the maximum standardized uptake (SUVmax) value. The 95% confidence intervals of the positive predictive value of piflufolastat F-18 (18F-DCFPyL) positron emission tomography scan and computed tomography (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. For lesions within the liver, a focal abnormal area of increased 18F-DCFPyL activity higher than the surrounding liver uptake (SUVmax more than x 1.2 times than the normal liver-SUV mean) will be considered positive. For lesions outside the liver, a positive lesion is defined as focal abnormal uptake higher than the blood pool or surrounding normal organ or soft tissue background.
Point Estimates of the Positive Predictive Value of Piflufolastat F-18 (18F-DCFPyL)	Baseline, post ablation, disease progression, an average of 3.87 months	Positive predictive value of the DCFPyL PET imaging agent is defined as the proportion of radiologically positive lesions (true positives) that were PET positive, over the radiologically (CT/MRI) positive lesions that were PET positive (true positives) added to the radiologically negative lesions that were PET positive (false positives). Point estimates and 95% confidence intervals of the positive predictive values of piflufolastat F-18 (18F-DCFPyL) positron emission tomography scan and computed tomography (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

Name	Time	Method
Lesion Level Sensitivity	Baseline, post ablation, and disease progression, an average of 3.87 months	Lesion level sensitivity is defined as true positive (TP)/\[TP+ false negative (FN\], being TP = true positive lesions (i.e., positron emission tomography (PET) positive lesions that are histologically positive) and FN = false negative lesions (i.e., PET negative lesions that are histologically positive) . The lesion level sensitivity of piflufolastat F-18 (18F-DCFPyL) positron emission tomography scan and a computed tomography (PET/CT) and CT/magnetic resonance imaging (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.
Lesion Level Specificity	Baseline, post ablation, and disease progression, an average of 3.87 months	Lesion level specificity is defined as true negative (TN)/\[TN+ false positive (FP\], being TN = true negative (i.e., positron emission tomography (PET) negative lesions that are histopathologically negative, and FP = false positive (i.e., PET positive lesions that are histopathologically negative). The lesion level specificity of piflufolastat F-18 (18F-DCFPyL) positron emission tomography scan and a computed tomography (PET/CT) and CT/magnetic resonance imaging (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.
Lesion Level Positive Predictive Value	Baseline, post ablation, and disease progression, an average of 3.87 months	Lesion level positive predictive value is defined as true positive (TP/\[TP+ false positive (FP\], being TP = true positive (i.e., positron emission tomography (PET) positive lesions that are histopathologically positive) and FP = false positive (i.e., PET positive lesions that are histopathologically negative) . The lesion level positive predictive value of piflufolastat F-18 (18F-DCFPyL) positron emission tomography scan and a computed tomography (PET/CT) and CT/magnetic resonance imaging (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 Piflufolastat F-18 (18F-DCFPyL) Positron Emission Tomography and Computed Tomography (PET/CT) Maximum Standardized Uptake Value (SUVmax) Between Pre- and Post-treatment	Pre- and post-treatment hepatocellular carcinoma (HCC) 18F-DCFPyL PET scans, an average of 3.2 months.	Change in 18F-DCFPyL PET/CT maximum standardized uptake value (SUVmax) between pre- and post-treatment tumor or tumor bed will be compared by paired Wilcoxon test for participants who undergo local treatment for hepatocellular carcinoma. Positive uptake is defined as a focal abnormal area of increased 18F-DCFPyL activity higher than the surrounding liver uptake standard update value (SUV)max more than x 1.2 times than the normal liver-SUV mean). Negative uptake is defined as tumor uptake less than adjacent background soft tissue, or less than blood pool for lymph nodes.

Trial Locations

Locations (1): National Institutes of Health Clinical Center
🇺🇸
Bethesda, Maryland, United States
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States