18F-FSPG PET in Imaging Patients With Liver Cancer Before Undergoing Surgery or Transplant

PET Imaging of Hepatocellular Carcinoma With 18F-FSPG

This clinical trial studies fluorine F 18 L-glutamate derivative BAY94-9392 (18F-FSPG) positron emission tomography (PET) in imaging patients with liver cancer before undergoing surgery or transplant. Diagnostic procedures, such as 18F-FSPG PET, may help find and diagnose liver cancer and find out how far the disease has spread.

Study Overview

• Status: Recruiting
• Conditions: Cholangiocarcinoma; Adult Hepatocellular Carcinoma; Resectable Hepatocellular Carcinoma; Benign Liver Tumor; Metastases to Liver
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Biological: Fluorine F 18 L-glutamate Derivative 18F-FSPG; Procedure: Positron Emission Tomography; Biological: Carbon C 11 Acetate; Biological: Fluorine F 18 2-deoxy-2-(18F)fluoro-D-glucose

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the relationship between 18F-FSPG PET/computed tomography (CT), pathology, and cancer metabolism in patients with suspected hepatocellular carcinoma (HCC) scheduled for liver resection surgery and orthotopic liver transplant (OLT).

II. To compare 18F-FSPG PET/CT with standard-of-care (SOC) diagnostic MRI imaging in patients with suspected HCC scheduled for liver resection surgery or OLT.

III. To compare the uptake of 18F-FSPG PET/CT with 11C-acetate PET/CT AND 18F-FDG PET/CT in suspected HCC and background liver in patients scheduled for liver resection surgery or OLT.

IV. To evaluate uptake of 18F-FSPG PET/CT in benign liver lesions compared to background.

V. To evaluate uptake of 18F-FSPG PET/CT in malignant non-HCC liver tumors.

OUTLINE:

Patients undergo 18F-FSPG PET and either carbon-11 (11C)-acetate PET or 18F-FDG PET scans within 4 weeks of surgery or OLT.

• Study Type: Interventional
• Enrollment (Estimated): 110
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Lesley Flynt, MD; Phone Number: 713-745-8760; Email: lflynt@mdanderson.org

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77090
      • Recruiting
      • MD Anderson Cancer Center
      • Contact: Lesley Flynt, MD; Email: lflynt@mdanderson.org
      • Principal Investigator: Lesley Flynt, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Diagnosis of HCC with one or more of the following:

   1. Liver mass with non-rim arterial phase hyperenhancement (APHE) and one of the following: 1) 10-19 mm with ≥2 additional major features according to LI-RADS criteria ("washout", enhancing "capsule", and/or threshold growth), 2) 10-19 mm with "washout" and visibility at antecedent ultrasound (US) but with no "capsule" or threshold growth, 3) 10-19 mm with ≥50% size increase in ≤6 months but with no "washout" or "capsule" or 4) ≥20 mm with ≥1 additional major feature according to LI-RADS criteria ("washout", enhancing "capsule", or threshold growth).
   2. Lesions that meet LI-RADS 4 criteria or
   3. Lesions that meet LI-RADS 5 criteria or
   4. Suggestive imaging findings plus AFP > 200 mg/dL or
   5. Tumor confirmed by arteriography or
   6. Pathologic confirmation of tumor or

2. Diagnosis of a benign abdominal or pelvic tumor with the following characteristics:

   1. Liver mass (≥ 1 cm) that has suggestive imaging findings of a benign liver mass (adenoma, hemangioma, focal nodular hyperplasia).
   2. Prior SOC MRI or CT of the benign lesion within 8 weeks of enrollment or

3. Diagnosis of a malignant non-HCC liver tumor with one or more of the following characteristics:

   1. Liver mass (≥ 1 cm) that is biopsy proven, MRI-confirmed, or CT-confirmed metastatic disease (metastatic colorectal cancer, metastatic pancreatic cancer).
   2. Liver mass (≥ 1 cm) that is a non-HCC primary malignancy (cholangiocarcinoma).
   3. Prior SOC MRI or CT of the malignant non-HCC liver tumor within 8 weeks of enrollment or

4. Diagnosis of oligometastatic solid tumors in the following disease sites: colorectal, sarcoma, lung, head and neck, ovarian, renal, melanoma, pancreatic, prostate, cervix, breast, uterine and cholangiocarcinoma undergoing local consolidative therapy.

   and

5. Each patient must have completed conventional imaging and staging and MRI or CT before initiation of the investigational PET studies.

   and

6. Patients with HCC must be a candidate for liver resection, orthotopic liver transplant (OLT), or Y90 radioembolization.

Exclusion Criteria:

1. Patients under the age of 18 will be excluded from this study.
2. Patients who have HCC or cholangiocarcinoma but are not candidates for liver resection surgery or OLT
3. Patients with a known prior malignancy who have received systemic chemotherapy within five years. Basal cell carcinoma of the skin, carcinoma in situ of the cervix, prior HCC, and patients with liver mass(es) proven to be metastatic disease are not excluded.
4. Pregnant and breastfeeding patients.
5. Patients with poorly controlled diabetes mellitus (fasting blood glucose level > 200 mg/dL).
6. Patients with a known Infiltrative variant of HCC.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Diagnostic (18F-FSPG PET); Patients undergo an 18F-FSPG PET scan within 4 weeks of surgery or OLT. Patients may also receive a second 18F-FSPG PET scan following standard-of-care treatment.	Other: Laboratory Biomarker Analysis; Correlative studies; Biological: Fluorine F 18 L-glutamate Derivative 18F-FSPG; Undergo 18F-FSPG PET scan; Other Names: BAY94-9392; Procedure: Positron Emission Tomography; Undergo 18F-FSPG, 11C-acetate, or 18F-FDG PET; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan
Experimental: Diagnostic (11C-Acetate PET or 18F-FDG PET); Patients may undergo either carbon-11 (11C)-Acetate PET or 18F-FDG PET scans within 4 weeks of surgery or OLT.	Other: Laboratory Biomarker Analysis; Correlative studies; Biological: Fluorine F 18 L-glutamate Derivative 18F-FSPG; Undergo 18F-FSPG PET scan; Other Names: BAY94-9392; Procedure: Positron Emission Tomography; Undergo 18F-FSPG, 11C-acetate, or 18F-FDG PET; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Biological: Carbon C 11 Acetate; Undergo 11C-acetate PET scan; Other Names: 11C-acetate; Biological: Fluorine F 18 2-deoxy-2-(18F)fluoro-D-glucose; Undergo 18F-FDG PET scan; Other Names: 18F-FDG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
18F-FSPG PET standardized uptake value (SUV)	The Standardized Uptake Value (SUV) for 18F-FSPG PET images will be determined in the hepatocellular carcinoma (HCC) tumor lesions, non-HCC liver tumors (benign), and background liver (normal tissue). These metrics include SUVmax, SUVpeak, or SUVmean and are common PET imaging measures.	Within 4 weeks of standard-of-care imaging, within 4 weeks of liver resection surgery, within 12 months of orthotopic liver transplant and prior to therapy
11C-acetate standardized uptake value (SUV)	The Standardized Uptake Value (SUV) for 11C-acetate PET images will be determined in the tumor lesions and background liver (normal tissue). These metrics include SUVmax, SUVpeak, or SUVmean and are common PET imaging measures.	Within 4 weeks of standard-of-care imaging, within 4 weeks of liver resection surgery, within 12 months of orthotopic liver transplant and prior to therapy
18F-FDG standardized uptake value (SUV)	The Standardized Uptake Value (SUV) for 18F-FDG PET images will be determined in the hepatocellular carcinoma (HCC) tumor lesions and background liver (normal tissue). These metrics include SUVmax, SUVpeak, or SUVmean and are common PET imaging measures.	Within 4 weeks of standard-of-care imaging, within 4 weeks of liver resection surgery, within 12 months of orthotopic liver transplant and prior to therapy
Pharmacokinetics of 18F-FSPG, 11C-acetate, and 18F-FDG	The pharmacokinetics of 18F-FSPG, 11C-acetate and 18F-FDG uptake will be determined using compartmental modeling of PET imaging data. Venous samples will be collected over the course of 18F-FSPG, 11C-acetate and 18F-FDG scans to confirm blood pool radioactivity, evaluate metabolism, and to calibrate image-derived input functions. We will also utilize blood samples collected prior to scanning to assay plasma levels of carbon-12 acetate and glucose in each patient to explore normalizing pharmacokinetic parameters across patients.	Within 4 weeks of standard-of-care imaging, within 4 weeks of liver resection surgery, within 12 months of orthotopic liver transplant and prior to therapy
Number of lesions	The number of lesions detected by 18F-FSPG PET will be determined and compared to the number of lesions detected by standard-of-care MRI, 11C-acetate PET, or 18F-FDG PET on a per patient basis.	Within 4 weeks of liver resection surgery, within 12 months of orthotopic liver transplant and prior to therapy
Sensitivity of 18F-FSPG PET imaging	Sensitivity is defined as the true positive rate. It is defined as true positive/(true positive + false negative). The determination of HCC status will be based on diagnostic pathology.	Within 4 weeks of standard-of-care imaging, within 4 weeks of liver resection surgery, within 12 months of orthotopic liver transplant and prior to therapy
Specificity of 18F-FSPG PET imaging	Specificity is defined as the true negative rate. It is defined as true negative/(true negative + false positive). The determination of HCC status will be based on diagnostic pathology.	Within 4 weeks of standard-of-care imaging, within 4 weeks of liver resection surgery, within 12 months of orthotopic liver transplant and prior to therapy
Diagnostic pathology	Tissue samples will be obtained for patients following either liver resection surgery or orthotopic liver transplant. Pathology will be performed on these tumor tissues as the gold-standard assessment to confirm the presence of HCC tumor. Histology will be correlated to PET imaging data.	After surgery; Through study completion, up to 4 years
Tumor grade	Tissue samples will be obtained for patients following either liver resection surgery or orthotopic liver transplant. Tumor grade will be determined from pathology of tissue samples and correlated to PET imaging data for 18F-FSPG, 11C-acetate and 18F-FDG PET. The concordance of 18F-FSPG PET/CT and 11C-acetate PET/CT or 18F-FSPG PET/CT and 18F-FDG PET/CT will be evaluated. This will determine whether 18F-FSPG can be used singularly in place of combined use of 11C-acetate PET/CT (which typically detects low grade HCC) and 18F-FDG PET/CT (which typically detects high grade HCC).	After surgery; Through study completion, up to 4 years
Immunohistochemistry	Tissue samples will be obtained for patients following liver resection surgery. The expression of immunohistochemical markers (ie. xC- and CD44) will be evaluated in these tumor tissues on an ordinal scale of 0, 1, 2 or 3 and correlated to 18F-FSPG PET imaging data. In addition, markers of inflammation and immune cell recruitment (ie. CD86, CD163, CD3), proliferation (Ki67), and apoptosis (Caspase 3) will also be evaluated and correlated to 18F-FSPG PET imaging data.	After surgery; Through study completion, up to 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolic profile	HCC tumor and non-cancerous liver tissue samples will be obtained for patients following liver resection surgery. Overall, tumoral tissue, peritumoral tissue and grossly normal surrounding liver will be evaluated. Metabolic profiles will be analyzed by mass spectrometry. The unbiased metabolomic phenome will be determined and correlated to 18F-FSPG PET.	After surgery; Through study completion, up to 4 years
Milan classification	Milan criteria will be applied to standard-of-care (SOC) MRI images. The number and size of lesions will be determined. A patient will be deemed to meet Milan criteria if they exhibit A) A single lesion 2 to 5 cm in diameter or B) Three or fewer tumors, each measuring 1 to 3 cm in diameter, and C) No evidence of extrahepatic involvement or microvascular invasion. The proportion of patients whose Milan classification by novel imaging classification changed following validation by histological confirmation will be determined.	Baseline prior to imaging and surgery

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Lesley Flynt, MD, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• MD Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2022
• Primary Completion (Estimated): May 31, 2025
• Study Completion (Estimated): May 31, 2025

Study Registration Dates

• First Submitted: February 6, 2015
• First Submitted That Met QC Criteria: February 26, 2015
• First Posted (Estimated): March 4, 2015

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 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; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Cholangiocarcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Radiopharmaceuticals; Cariostatic Agents; Fluorodeoxyglucose F18; Fluorides
• Other Study ID Numbers: 2020-1084; NCI-2015-00184 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U24CA220325 (U.S. NIH Grant/Contract)

Drug and device information, study documents

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