68Ga-PSMA-Dual-Contrast PET/MRI or PET/CT for Early Detection of Liver Cancer

Early Detection, Accurate Staging, and Biologic Characterization of HCC With Hybrid 68Ga-PSMA-Dual -Contrast PET/MRI and PET/CT Using Cyclotron-Produced 68Ga

This phase II trial studies how well 68Ga-PSMA PET/MRI or PET/CT works in early detection of liver cancer. 68Gallium-PSMA is a radioactive tracer designed to circulate through the body and attach itself to the prostate- specific membrane antigen (PSMA) protein on liver cancer cells. Magnetic resonance imaging (MRI) is a scan that uses magnetic and radio waves to produce detailed structural information of the organs, tissues, and structures within the body. Positron emission tomography (PET) is 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 (tracer) to show this activity. Computed tomography (CT) scan uses X-rays to create images of the bones and internal organs within your body. Combining a PET scan with an MRI or CT scan may help make the images easier to interpret. This trial may help determine if 68Ga- PSMA PET/MRI or PET/CT can improve upon the diagnosis and management of liver cancer in the future.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Gallium Ga 68 Gozetotide; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the feasibility and diagnostic performance of gallium Ga 68 gozetotide (68Ga PSMA)-dual contrast PET/MRI for detection and staging of hepatocellular carcinoma (HCC), and to compare it with standard-of-care (SOC) imaging.

II. To identify the biologic correlates of biomarkers derived from 68Ga PSMA-dual contrast PET/MRI with histopathology features and PSMA immunostaining of HCC.

OUTLINE:

Patients receive 68Ga-PSMA intravenously (IV) over 90 minutes. Patients then undergo PET/MRI over 60 minutes or PET/CT over 30 minutes.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic in Rochester
      • Principal Investigator: Ajit H. Goenka, M.D.
      • Contact: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with either an imaging diagnosis of Hepatocellular carcinoma (HCC) by Computed Tomography (CT) or Magnetic Resonance Imaging MRI (Liver Imaging Reporting and Data System [LI-RADS] 5) confirmed by a board-certified abdominal radiologist, or with biopsy-proven HCC
• Subjects who may undergo hepatic surgical resection, liver transplant, or hepatic locoregional therapy (LRT) (e.g., ablation, embolization, etc.)
• No prior treatment for index HCC lesion (surgical resection, liver transplant, hepatic locoregional therapy arm). Patients that have been previously treated with HCC, but have new or reoccurring untreated lesions, are included in the study.
• Male or female with age greater than 18 years, with the capacity and willingness to provide written informed consent.

Exclusion Criteria:

• Patients 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 positron emission tomography [PET]/MRI)
• Patients with glomerular filtration rate (GFR) < 30 ml/min/1.73m^2, on dialysis, or with acute kidney injury
• Pregnant and/or breast-feeding patients. A negative pregnancy test within 48 hours of the PET scan
• Patients with higher than the weight/size limitations of PET/MRI or PET/CT scanner
• Subjects with history of allergic response to Eovist or Gadavist
• Subjects with known history of claustrophobia
• Subjects with GFR < 30 ml/min/1.73m^2, on dialysis, or with acute kidney injury
• Subjects with a history of severe hypersensitivity to Eovist or Gadavist

• Patients with contraindication to MRI (relevant to PET/MRI):

  • Patients who have a heart pacemaker
  • Patients who have a metallic foreign body (metal sliver) in their eye, or who have an aneurysm clip in their brain
  • Patients who have implanted devices with magnets
  • Patients who have other implanted electronic devices
  • Patients who have deep brain stimulator
  • Patients who have vagal nerve stimulator
  • Patients with cochlear (ear) or auditory implants

PSMA PET/CT will be an alternative in this study for patients who are unable to undergo PET/MRI for any reason but are otherwise eligible for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Diagnostic (68Ga-PSMA PET/MRI or PET/CT); Patients receive 68Ga-PSMA IV over 90 minutes. Patients then undergo PET/MRI over 60 minutes or PET/CT over 30 minutes.

Drug: Gallium Ga 68 Gozetotide; Given IV; Other Names: (68)Ga labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC; (68)Ga-labeled Glu-urea-Lys(Ahx)-HBED-CC; (68)Ga-PSMA Ligand Glu-urea-Lys(Ahx)-HBED-CC; (68)Gallium-PSMA Ligand Glu-urea-Lys(Ahx)-HBED-CC; (68Ga)Glu-urea-Lys(Ahx)-HBED-CC; 68Ga-DKFZ-PSMA-11; 68Ga-HBED-CC-PSMA; 68Ga-labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC; 68Ga-PSMA; 68Ga-PSMA-11; 68Ga-PSMA-HBED-CC; [68Ga] Prostate-specific Membrane Antigen 11; [68Ga]GaPSMA-11; Ga PSMA; Ga-68 labeled DKFZ-PSMA-11; Ga-68 labeled PSMA-11; GA-68 PSMA-11; Gallium Ga 68 PSMA-11; Gallium Ga 68-labeled PSMA-11; GALLIUM GA-68 GOZETOTIDE; Gallium-68 PSMA; Gallium-68 PSMA Ligand Glu-urea-Lys(Ahx)-HBED-CC; GaPSMA; PSMA-HBED-CC GA-68; Procedure: Computed Tomography; Undergo PET/CT; Other Names: CT; CAT; CAT Scan; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Procedure: Magnetic Resonance Imaging; Undergo PET/MRI; Other Names: MRI; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; PET/MRI or PET/CT; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic performance of 68Ga-PSMA-dual contrast	Using surgical histopathology of resected or biopsied lesions and routine imaging surveillance (for lesions that cannot be resected or biopsied) as the gold standard, we will estimate the diagnostic performance (lesion-level sensitivity, specificity measures, and corresponding 95% confidence intervals) of PET/MRI for hepatic lesions and extra-hepatic metastases, and compare it with standard-of-care (SOC) imaging (MRI and CT) to identify the incremental benefit of PET/MRI.	Up to 6 weeks
Correlate biomarkers derived from PET/MRI with PSMA immuno-histochemical (IHC) grading	PSMA stained sections will be evaluated by light microscopy for PSMA localization and the entire section reviewed to determine percentage area of PSMA immunostaining as follows: 0 = no staining, 1 = < 5% staining, 2= 5 to 30% staining, 3 = 31 to 60% staining, and 4 = 61-100% staining. Grades 0-2 will be grouped as 'low PSMA expression' and grades 3 and 4 will be grouped as 'high PSMA expression'	Up to 6 weeks
Correlate biomarkers derived from PET/MRI with PSMA immuno-histochemical (IHC) grading	Intensity of PSMA uptake in hepatic lesions on PET will be graded as follows: grade 1: uptake < normal liver; grade 2: uptake = normal liver; grade 3: uptake > normal liver; grade 4: uptake > spleen or kidneys. For correlation with PSMA IHC scoring, grades 1 and 2 on PET/MRI will be grouped as 'low PSMA expression'. Conversely, grades 3 and 4 will be grouped as 'high PSMA expression'.	Up to 6 weeks

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI); United States Department of Defense
• Investigators: Principal Investigator: Ajit H. Goenka, M.D., Mayo Clinic in Rochester

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2021
• Primary Completion (Estimated): January 10, 2025
• Study Completion (Estimated): July 7, 2025

Study Registration Dates

• First Submitted: February 11, 2021
• First Submitted That Met QC Criteria: February 16, 2021
• First Posted (Actual): February 21, 2021

Study Record Updates

• Last Update Posted (Actual): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 17, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Anticoagulants; Chelating Agents; Sequestering Agents; Calcium Chelating Agents; Edetic Acid; Gallium 68 PSMA-11
• Other Study ID Numbers: 20-006433; P30CA015083 (U.S. NIH Grant/Contract); NCI-2021-01092 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No