PSMA PET/MRI or PSMA PET/CT for Evaluation of Liver Cancer

Study Overview
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Brief Summary
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This clinical trial evaluates whether 68Ga-PSMA PET/MRI or PET/CT can improve upon the diagnosis and management of liver cancer. MRI stands for magnetic resonance imaging, a scan that uses magnetic and radio waves to produce detailed structural information of the organs, tissues and structures within the body. PET stands for positron emission tomography, an imaging test that helps to measure the information about functions of tissues and organs within the body. A PET scan uses a radioactive drug (radiotracer) to show this activity. CT scan uses X-rays to create images of the bones and internal organs within the body. In patients that have been diagnosed with liver cancer, a protein called prostate specific membrane antigen (PSMA) appears in large amounts on the surface of the cancerous cells. The radioactive chemical compound (68Ga-PSMA) has been designed to circulate through the body and attach itself to the PSMA protein on liver cancer cells. 68Ga-PSMA PET/MRI or PET/CT may be better in diagnosing and managing liver cancer.

Detailed Description
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PRIMARY OBJECTIVE: I. To evaluate diagnostic performance of gallium Ga 68 gozetotide (68Ga-PSMA-dual contrast [Gadavist and gadoxetate]) positron emission tomography (PET)/magnetic resonance imaging (MRI) OR PET/computed tomography (CT) for hepatocellular carcinoma (HCC) using surgical histopathology (either resection, transplant or biopsy specimens) or Liver Imaging and Reporting Data System (LI-RADS) categorization as gold standard. II. To evaluate treatment response after locoregional therapy or systemic therapy in HCC using 68Ga-PSMA uptake at PET (qualitative & semi-quantitative measures) and to compare it with standard CT/MRI morphologic and post-contrast enhancement based response criteria (modified Response Evaluation Criteria in Solid Tumors [mRECIST] and LI-RADS-treatment response [LR-TR] algorithm). III. To determine association between PSMA uptake in HCCs at PET with tissue prostate specific membrane antigen (PSMA) expression using immunohistochemistry or serum/plasma PSMA expression using enzyme-linked immunosorbent assay (ELISA). OUTLINE: Patients receive gallium Ga 68 gozetotide intravenously (IV), and undergo PET/MRI over 60 minutes or PET/CT over 30 minutes at baseline and 12 weeks after completion of hepatic locoregional therapy or 8-12 weeks after completion of systemic therapy. Patients undergoing hepatic locoregional therapy may also undergo a liver biopsy.

Official Title
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Development and Validation of Innovative Hybrid Molecular Imaging, 68Ga-PSMA-Dual Contrast PET/MRI and 68Ga-PSMA PET/CT, to Transform the Care of Patients With Hepatocellular Carcinoma

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Procedure: Biopsy
* Procedure: Computed Tomography
* Drug: Gallium Ga 68 Gozetotide
* Procedure: Magnetic Resonance Imaging
* Procedure: Positron Emission Tomography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with either an imaging diagnosis of HCC by CT or MRI (LI-RADS 5) confirmed by a board-certified abdominal radiologist, or with biopsy-proven HCC Subjects who may undergo hepatic surgical resection, liver transplant, hepatic locoregional therapy (ablation, embolization, etc.) or systemic therapy No prior treatment for index HCC lesion (surgical resection, liver transplant, hepatic locoregional therapy arm) For the systemic therapy arm, patients who have had unequivocal progression after prior locoregional therapy (LRT) and/or those undergoing de novo systemic therapy in view of advanced HCC at diagnosis Male or female with age greater than 18 years, with the capacity and willingness to provide a written informed consent Exclusion Criteria: Subjects requiring emergent surgery for a ruptured/bleeding HCC Bilirubin > 3.0 mg/dL, which is a contraindication for Gadoxetate, the MRI contrast agent (relevant to PET/MRI) Pregnant and/or breast-feeding subjects. A negative pregnancy test within 48 hours of the PET scan Subjects with higher than the weight/size limitations of PET/MRI or PET/CT scanner Subjects with contraindication to MRI (relevant to PET/MRI): Subjects who have a heart pacemaker Subjects who have a metallic foreign body (metal sliver) in their eye, or who have an aneurysm clip in their brain Subjects who have implanted devices with magnets Subjects who have other implanted electronic devices Subjects who have deep brain stimulator Subjects who have vagal nerve stimulator Subjects with cochlear (ear) or auditory implants

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diagnostic (gallium Ga 68 gozetotide PET/MRI, PET/CT, biopsy)<br>Patients receive gallium Ga 68 gozetotide IV, and undergo PET/MRI over 60 minutes or PET/CT over 30 minutes at baseline and 12 weeks after completion of hepatic locoregional therapy or 8-12 weeks after completion of systemic therapy. Patients undergoing hepatic locoregional therapy may also undergo a liver biopsy. | Procedure: Biopsy<br>* Undergo biopsy<br>* Other names: Bx;Procedure: Computed Tomography<br>* Undergo CT<br>* Other names: tomography;Drug: Gallium Ga 68 Gozetotide<br>* Given IV<br>* Other names: PSMA-HBED-CC GA-68;Procedure: Magnetic Resonance Imaging<br>* Undergo MRI<br>* Other names: Nuclear Magnetic Resonance Imaging;Procedure: Positron Emission Tomography<br>* Undergo PET<br>* Other names: PT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic performance of 68Ga-PSMA-dual contrast (gadavist and gadoxetate) positron emission tomography/magnetic resonance imaging (PET/MRI), or 68Ga-PSMA positron emission tomography/computed tomography (PET/CT) | Using surgical histopathology (either resection or transplant specimens) or Liver Imaging and Reporting Data System (LI-RADS[R]) categorization as gold standard. | At 3 months after completion of hepatic locoregional therapy or systemic therapy | 
| Treatment response after locoregional therapy in hepatocellular carcinoma (HCC) | Using 68Ga-PSMA uptake at PET (qualitative & semi-quantitative measures) compared with standard CT/MRI morphologic and post-contrast enhancement based response criteria (modified Response Evaluation Criteria in Solid Tumors and LI-RADS-treatment response [LR-TR] algorithm). | Completion of locoregional therapy (up to 3 months) | 
| Association between prostate specific membrane antigen (PSMA) uptake in hepatocellular carcinoma at PET with tissue PSMA expression | Assessed using immunohistochemistry, serum/plasma PSMA expression using enzyme-linked immunosorbent assay or serum HCC tumor markers. | Up to 3 years |