Clinical trial NCT07019844: PSMA PET for the Staging and Management of Hepatocellular Carcinoma
Official title: Addition of F18-Piflufolastat PET/CT to Cross-Sectional Imaging for the Staging and Management of Hepatocellular Carcinoma
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hepatocellular Carcinoma (HCC)
Lead sponsor: Miami VA Healthcare System
Sponsor class: FED
First posted: 2025-06-13
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: This study will recruit 90 veterans from the VHA with HCC, and no non-veteran participants. This will include 30 participants with LR-3 and 4 lesions detected during surveillance (Aim 1), 30 treatment naïve participants towards Aim 2, and 30 treatment experienced participants for Aim 3. In addition, 10 participants out of the 60 who are recruited for aims 2 and 3 are projected to have indeterminate nodules, increasing the number of participants with indeterminate nodules to 40. West Palm Beach and Orlando VA patients who are evaluated at the Miami VA, will be approached for study recruitment. These veterans will continue to be co-managed by the Miami VA and the local VA teams after undergoing treatment in Miami.

Brief summary: This prospective, single-center study evaluates the clinical utility of F18-Piflufolastat (PSMA) PET/CT when added to conventional cross-sectional imaging for patients with suspected or confirmed hepatocellular carcinoma (HCC). The study aims to determine whether PSMA PET/CT improves diagnostic accuracy for indeterminate liver lesions (LI-RADS 3 and 4), enhances staging precision in treatment-naïve patients, and provides more accurate assessment of treatment response in patients undergoing locoregional therapy (LRT). The goal is to assess how PSMA PET/CT may impact clinical decision-making, staging, and management of HCC across multiple stages of disease.

Detailed description: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and a leading cause of cancer-related mortality worldwide. Accurate diagnosis, staging, and treatment response assessment are critical for optimal management of patients with HCC. However, conventional imaging modalities, such as contrast-enhanced CT and MRI, have limitations in characterizing indeterminate liver lesions and in detecting intrahepatic or extrahepatic disease, particularly in the context of post-treatment changes.

This prospective, single-center study investigates the added value of F18-Piflufolastat (PSMA) PET/CT in the evaluation and management of patients with suspected or confirmed HCC. PSMA (Prostate-Specific Membrane Antigen) is a cell surface protein that, while originally characterized in prostate cancer, has demonstrated overexpression in the neovasculature of a variety of solid tumors, including HCC. F18-Piflufolastat is a radiotracer that targets PSMA, allowing for enhanced molecular imaging.

Participants will undergo PSMA PET/CT imaging in addition to standard-of-care imaging (CT and/or MRI). The study is designed to address three primary clinical questions:

1. Diagnosis: Does the addition of PSMA PET/CT improve characterization of indeterminate liver lesions (e.g., LI-RADS 3 or 4)?
2. Staging: Can PSMA PET/CT improve the accuracy of disease staging in treatment-naïve patients by detecting intrahepatic or extrahepatic disease not visualized on conventional imaging?
3. Treatment Response: In patients who have undergone locoregional therapy (LRT), does PSMA PET/CT provide more precise assessment of viable tumor tissue compared to standard imaging? Data collected will include imaging results, histopathological confirmation when available, changes in clinical management prompted by PSMA PET/CT findings, and correlation with clinical outcomes. By evaluating the clinical utility of PSMA PET/CT across multiple phases of the disease course, this study aims to inform future diagnostic algorithms and treatment planning strategies in patients with HCC.

Eligibility criteria: Inclusion Criteria:

* 1. adult patients age\>18 years from the VA medical system; 2. Treatment-naïve patients with HCC with BCLC B or C disease.

Exclusion Criteria:

* 1. Patients with renal dysfunction or contrast allergy that precludes contrast enhanced cross sectional imaging; 2. Patients with presence of active primary malignancy other than HCC and non-melanoma skin cancer in the past 3 years.

Primary outcomes:
measure: 1. Change in Diagnostic Classification of Indeterminate Lesions (LI-RADS 3/4) After PSMA PET/CT; 2. Change in Clinical Staging in Treatment-Naïve Patients; 3. Change in Assessment of Treatment Response Following Locoregional Therapy
timeFrame: 1. Within 30 days of PET/CT imaging; 2. Within 30 days of PET/CT imaging; 3. Within 30 days of post-treatment imaging
Secondary outcomes:
measure: 1. Change in Clinical Management Based on PSMA PET/CT Findings; 2. Change in Clinical Staging in Treatment-Naïve Patients; 3. Change in Assessment of Treatment Response Following Locoregional Therapy
timeFrame: 1. Within 30 days of PET/CT imaging; 2. Within 30 days of PET/CT imaging; 3. Within 30 days of post-treatment imaging
Other outcomes:
measure: 1. Inter-reader Agreement on PSMA PET/CT Interpretation; 2. Correlation Between PSMA Uptake and Histopathologic Features
timeFrame: 1. Within 30 days of imaging; 2. Up to 90 days post-imaging (when surgical specimens are available)
Locations:
city: Miami
country: United States
facility: Miami VA Healthcare System
state: Florida
Study officials:
affiliation: Miami VA Healthcare System
name: Binu John, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: John BV, Aubuchon S, Dahman B, Konjeti VR, Heuman D, Hubert J, Thomas S, Deng Y, Solomon C, Sundaram LT, Love E, Singal AG, Tatum JL. Addition of [18 F]Fluorodeoxyglucose Positron Emission Tomography With Computed Tomography to Cross-Sectional Imaging Improves Staging and Alters Management in Hepatocellular Carcinoma. Liver Transpl. 2020 Jun;26(6):774-784. doi: 10.1002/lt.25743. Epub 2020 May 8.