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

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ClinicalTrials.gov Identifier: NCT02379377
Recruitment Status : Not yet recruiting
First Posted : March 4, 2015
Last Update Posted : September 10, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Adult Hepatocellular Carcinoma Resectable Hepatocellular Carcinoma Cholangiocarcinoma Benign Liver Tumor Metastases to Liver Biological: Fluorine F 18 L-glutamate Derivative 18F-FSPG Biological: Carbon C 11 Acetate Procedure: Positron Emission Tomography Other: Laboratory Biomarker Analysis Biological: Fluorine F 18 2-deoxy-2-(18F)fluoro-D-glucose Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Cohorts A and B are Parallel. Cohorts C and D are Single Group.
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: PET Imaging of Hepatocellular Carcinoma With 18F-FSPG
Estimated Study Start Date : October 1, 2021
Estimated Primary Completion Date : May 31, 2024
Estimated Study Completion Date : May 31, 2025

Resource links provided by the National Library of Medicine


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.
Biological: Fluorine F 18 L-glutamate Derivative 18F-FSPG
Undergo 18F-FSPG PET scan
Other Name: 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

Other: Laboratory Biomarker Analysis
Correlative studies

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.
Biological: Fluorine F 18 L-glutamate Derivative 18F-FSPG
Undergo 18F-FSPG PET scan
Other Name: BAY94-9392

Biological: Carbon C 11 Acetate
Undergo 11C-acetate PET scan
Other Name: 11C-acetate

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

Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Fluorine F 18 2-deoxy-2-(18F)fluoro-D-glucose
Undergo 18F-FDG PET scan
Other Name: 18F-FDG




Primary Outcome Measures :
  1. 18F-FSPG PET standardized uptake value (SUV) [ Time Frame: 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 ]
    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.

  2. 11C-acetate standardized uptake value (SUV) [ Time Frame: 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 ]
    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.

  3. 18F-FDG standardized uptake value (SUV) [ Time Frame: 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 ]
    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.

  4. Pharmacokinetics of 18F-FSPG, 11C-acetate, and 18F-FDG [ Time Frame: 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 ]
    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.

  5. Number of lesions [ Time Frame: Within 4 weeks of liver resection surgery, within 12 months of orthotopic liver transplant and prior to therapy ]
    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.

  6. Sensitivity of 18F-FSPG PET imaging [ Time Frame: 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 ]
    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.

  7. Specificity of 18F-FSPG PET imaging [ Time Frame: 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 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.

  8. Diagnostic pathology [ Time Frame: After surgery; Through study completion, up to 4 years ]
    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.

  9. Tumor grade [ Time Frame: After surgery; Through study completion, up to 4 years ]
    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).

  10. Immunohistochemistry [ Time Frame: After surgery; Through study completion, up to 4 years ]
    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.


Secondary Outcome Measures :
  1. Metabolic profile [ Time Frame: After surgery; Through study completion, up to 4 years ]
    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.

  2. Milan classification [ Time Frame: Baseline prior to imaging and surgery ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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. Suggestive imaging findings plus AFP > 200 mg/dL; or
    3. Tumor confirmed by arteriography. or
  2. Diagnosis of a benign liver 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 of the benign liver lesion within 4 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 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 of the malignant non-HCC liver tumor within 4 weeks of enrollment

and

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

and

4. Patients with HCC or cholangiocarcinoma must be a candidate for liver resection or orthotopic liver transplant (OLT)

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02379377


Contacts
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Contact: Lesley Flynt, MD 713-745-8760 lflynt@mdanderson.org

Locations
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United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77090
Contact: Lesley Flynt, MD       lflynt@mdanderson.org   
Principal Investigator: Lesley Flynt, MD         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Lesley Flynt, MD M.D. Anderson Cancer Center
Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02379377    
Other Study ID Numbers: 2020-1084
NCI-2015-00184 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
U24CA220325 ( U.S. NIH Grant/Contract )
First Posted: March 4, 2015    Key Record Dates
Last Update Posted: September 10, 2021
Last Verified: September 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Cholangiocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Carcinoma
Carcinoma, Hepatocellular
Adenocarcinoma
Digestive System Diseases
Liver Diseases
Fluorodeoxyglucose F18
Fluorides
Radiopharmaceuticals
Molecular Mechanisms of Pharmacological Action
Cariostatic Agents
Protective Agents
Physiological Effects of Drugs