18F-FSPG PET/CT in Imaging Patients With Newly Diagnosed Lung Cancer or Indeterminate Pulmonary Nodules

Sponsor
Vanderbilt-Ingram Cancer Center (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT02448225
Collaborator
National Cancer Institute (NCI) (NIH)
46
2
1
86.5
23
0.3

Study Details

Study Description

Brief Summary

This clinical trial compares fluorine F 18 L-glutamate derivative BAY94-9392 (18F-FSPG) positron emission tomography (PET)/computed tomography (CT) to the standard of care fluorodeoxyglucose F-18 (18F-FDG) PET/CT in imaging patients with newly diagnosed lung cancer or indeterminate pulmonary nodules. PET/CT uses a radioactive glutamate (one of the common building blocks of protein) called 18F-FSPG which may be able to recognize differences between tumor and healthy tissue. Since tumor cells are growing, they need to make protein, and other building blocks, for cell growth that are made from glutamate and other molecules. PET/CT using a radioactive glutamate may be a more effective method of diagnosing lung cancer than the standard PET/CT using a radioactive glucose (sugar), such as 18F-FDG.

Condition or Disease Intervention/Treatment Phase
  • Procedure: Computed Tomography
  • Procedure: Computed Tomography
  • Radiation: fluorodeoxyglucose F-18
  • Drug: Fluorine F 18 L-glutamate Derivative BAY94-9392
  • Other: Laboratory Biomarker Analysis
  • Procedure: Positron Emission Tomography
  • Procedure: Positron Emission Tomography (PET)
Phase 2

Detailed Description

PRIMARY OBJECTIVES:
  1. To compare the imaging characteristics of 18F-FSPG PET/CT with standard-of-care, 18F-FDG PET/CT.

  2. To compare the imaging characteristics of 18F-FSPG PET/CT to standard-of-care 18F-FDG PET/CT in patients with newly diagnosed lung cancer.

  3. To determine whether 18F-FSPG uptake in lung cancer can be predicted based on correlation with CD44 and amino acid transport system xc- (xC-) expression in surgical pathology specimens.

OUTLINE:

Patients undergo 18F-FDG PET/CT scan per standard of care. Within 15 working days, patients also undergo 18F-FSPG PET scan over 60 minutes followed by an 18F-FSPG PET/CT scan over 30 minutes.

After completion of study, patients are followed up for 2 years if needed for diagnosis.

Study Design

Study Type:
Interventional
Actual Enrollment :
46 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Diagnostic
Official Title:
PET Imaging of Lung Cancer and Indeterminate Pulmonary Nodules With 18F-FSPG
Actual Study Start Date :
Jun 16, 2015
Actual Primary Completion Date :
Aug 2, 2021
Anticipated Study Completion Date :
Aug 31, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Diagnostic (18F-FDG PET/CT, 18F-FSPG PET/CT)

Patients undergo 18F-FDG PET/CT scan per standard of care. Within 15 working days, patients also undergo 18F-FSPG PET scan over 60 minutes followed by an 18F-FSPG PET/CT scan over 30 minutes.

Procedure: Computed Tomography
Undergo 18F-FDG PET/CT - standard of care
Other Names:
  • CAT
  • CAT Scan
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT
  • CT SCAN
  • tomography
  • Procedure: Computed Tomography
    Undergo 18F-FSPG PET/CT
    Other Names:
  • CAT
  • CAT Scan
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT
  • CT SCAN
  • tomography
  • Radiation: fluorodeoxyglucose F-18
    Undergo 18F-FDG PET/CT - standard of care
    Other Names:
  • 18FDG
  • FDG
  • Fluorine-18 2-Fluoro-2-deoxy-D-Glucose
  • Drug: Fluorine F 18 L-glutamate Derivative BAY94-9392
    Undergo 18F-FSPG PET/CT
    Other Names:
  • (S)-4-(3-18F-fluoropropyl)-L-glutamic Acid
  • 18F-FSPG
  • BAY94-9392
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Procedure: Positron Emission Tomography
    Undergo 18F-FDG PET/CT - standard of care
    Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET SCAN
  • Positron Emission Tomography Scan
  • proton magnetic resonance spectroscopic imaging
  • Procedure: Positron Emission Tomography (PET)
    Undergo 18F-FSPG PET/CT
    Other Names:
  • Medical Imaging, Positron Emission Tomography
  • Positron Emission Tomography Scan
  • proton magnetic resonance spectroscopic imaging
  • Outcome Measures

    Primary Outcome Measures

    1. Ability of 18F-FSPG PET/CT to Discriminate Benign From Malignant Nodules [Up to 2 years]

      Sensitivity, specificity, overall accuracy and receiver operating characteristic (ROC) curves will be generated and compared for both 18F-FDG and 18F-FSPG tests. Sensitivity is the proportion of High(positive) among cancer patients. Specificity is the proportion of low(negative) among benign tumors. Accuracy is the proportion of correctly diagnosed among analyzed patients. Area under the curve(AUC) is the area under the ROC curve, which is the plot of sensitivity by 1-specificity.

    Secondary Outcome Measures

    1. CD44 and xC- Expression Levels in Tissue Samples(0-3) [Up to 2 years]

      The level of expression of xCT and CD44 proteins in the cytoplasmic membrane of tumor cells were examined by an experienced pathologist who was blinded to any patient and imaging information. The percentage of tumor cells positive for the marker and the intensity of staining were evaluated, the latter using a scale of 0 (none), 1+ (weak), 2+ (intermediate), and 3+ (strong) with a sample being reported as positive if greater than 10% of the tumor cells in the sample were positively stained with any intensity.

    2. Uptake of 18F-FSPG (Expressed in Maximal Standardized Uptake Value [SUV] Within the Tumor) [Up to 2 years]

      Maximum standardized uptake values (SUVmax) were normalized to lean body mass and measured with a 1 cm diameter round region of interest over the area of greatest uptake in the lesion being measured.

    3. Ability of 18F-FSPG PET/CT to Stage of Lung Cancer (Metastatic or Not) [Up to 2 years]

      Sensitivity, specificity, overall accuracy and ROC curves will be generated and compared for both 18F-FDG and 18F-FSPG tests. Wilcoxon rank-sum or Kruskal-Wallis tests will be applied for the group comparisons of the biodistribution characteristics of 18F-FDG and 18F-FSPG tests. Sensitivity is the proportion of High(positive) among cancer patients. Specificity is the proportion of low(negative) among benign tumors. Accuracy is the proportion of correctly diagnosed among all patients. Area under the curve(AUC) is the area under the ROC curve.

    Other Outcome Measures

    1. Uptake of 18F-FSPG (Expressed in Maximal Standardized Uptake Value [SUV] Within the [Up to 2 years]

      Descriptive statistics, including means, standard deviations, and ranges for continuous

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    40 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Have an indeterminate untreated pulmonary nodule (IPN) (7-30 mm diameter) on CT, or an indeterminate lung mass (> 30 mm diameter), without prior examinations that establish that the lesion has been stable for two or more years, untreated.

    or

    • Have a newly diagnosed, untreated primary lung cancer diameter 7 mm or more.

    • Be able to give informed consent, which will include a layman's explanation of the estimated amount of additional radiation that the patient will receive from the investigational PET/CT scan using 18F-FSPG

    • Must agree at the time of study entry to undergo clinically indicated biopsy(ies) or a 24-month period of follow-up, as needed, to resolve the etiology of their IPN(s) or lung mass(es).

    Exclusion Criteria:
    • Pregnant or lactating patients will be excluded, as will females of childbearing potential who refuse to undergo a serum or urinary beta-HCG pregnancy test the day of either the 18F-FSPG or the 18F-FDG PET/CT scans, in accordance with the standard policy of the Medical Imaging Service at our facility. Women who have experienced 24 consecutive months of amenorrhea, have reached at least 60 years of age, or have had a tubal ligation or hysterectomy documented in their medical records are considered not to be of childbearing potential for the purposes of this protocol

    • Patients with a body weight of 400 pounds or more or a body habitus or disability that will not permit the imaging protocol to be performed

    • A recognized active lung infection

    • Previous systemic or radiation treatment for cancer of any type within 1 year

    • For patients who do not have a tissue diagnosis:

    • Non-oncologic severe co-morbidities suggesting a life span of less than two years if not treated, as determined by the potential subject's treating physician.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Tennessee Valley Health System Nashville Nashville Tennessee United States 37212
    2 Vanderbilt-Ingram Cancer Center Nashville Tennessee United States 37232

    Sponsors and Collaborators

    • Vanderbilt-Ingram Cancer Center
    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Chirayu Shah, MD, Vanderbilt-Ingram Cancer Center

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Chirayu Shah, Associate Professor of Clinical Radiology, Vanderbilt-Ingram Cancer Center
    ClinicalTrials.gov Identifier:
    NCT02448225
    Other Study ID Numbers:
    • VICC THO 1524
    • NCI-2015-00748
    • P30CA068485
    First Posted:
    May 19, 2015
    Last Update Posted:
    Aug 1, 2022
    Last Verified:
    Jul 1, 2022

    Study Results

    Participant Flow

    Recruitment Details This study enrolled 46 patients between two clinical sites (15 at Veterans Affairs-Tennessee Valley Health System Nashville, TN and 31 at Vanderbilt University Medical Center, Nashville, TN). The enrollment period was 6/16/15 to 1/5/21.
    Pre-assignment Detail
    Arm/Group Title Diagnostic (18F-FDG PET/CT, 18F-FSPG PET/CT)
    Arm/Group Description Patients undergo 18F-FDG PET/CT scan per standard of care. Within 15 working days, patients also undergo 18F-FSPG PET scan over 60 minutes followed by an 18F-FSPG PET/CT scan over 30 minutes. Computed Tomography: Undergo 18F-FDG PET/CT - standard of care Computed Tomography: Undergo 18F-FSPG PET/CT fluorodeoxyglucose F-18: Undergo 18F-FDG PET/CT - standard of care Fluorine F 18 L-glutamate Derivative BAY94-9392: Undergo 18F-FSPG PET/CT Laboratory Biomarker Analysis: Correlative studies Positron Emission Tomography: Undergo 18F-FDG PET/CT - standard of care Positron Emission Tomography (PET): Undergo 18F-FSPG PET/CT
    Period Title: Overall Study
    STARTED 46
    COMPLETED 26
    NOT COMPLETED 20

    Baseline Characteristics

    Arm/Group Title Diagnostic (18F-FDG PET/CT, 18F-FSPG PET/CT)
    Arm/Group Description Patients undergo 18F-FDG PET/CT scan per standard of care. Within 15 working days, patients also undergo 18F-FSPG PET scan over 60 minutes followed by an 18F-FSPG PET/CT scan over 30 minutes. Computed Tomography: Undergo 18F-FDG PET/CT - standard of care Computed Tomography: Undergo 18F-FSPG PET/CT fluorodeoxyglucose F-18: Undergo 18F-FDG PET/CT - standard of care Fluorine F 18 L-glutamate Derivative BAY94-9392: Undergo 18F-FSPG PET/CT Laboratory Biomarker Analysis: Correlative studies Positron Emission Tomography: Undergo 18F-FDG PET/CT - standard of care Positron Emission Tomography (PET): Undergo 18F-FSPG PET/CT
    Overall Participants 46
    Age (Count of Participants)
    <=18 years
    0
    0%
    Between 18 and 65 years
    23
    50%
    >=65 years
    23
    50%
    Sex: Female, Male (Count of Participants)
    Female
    16
    34.8%
    Male
    30
    65.2%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    3
    6.5%
    Not Hispanic or Latino
    43
    93.5%
    Unknown or Not Reported
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    1
    2.2%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    5
    10.9%
    White
    40
    87%
    More than one race
    0
    0%
    Unknown or Not Reported
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    46
    100%

    Outcome Measures

    1. Primary Outcome
    Title Ability of 18F-FSPG PET/CT to Discriminate Benign From Malignant Nodules
    Description Sensitivity, specificity, overall accuracy and receiver operating characteristic (ROC) curves will be generated and compared for both 18F-FDG and 18F-FSPG tests. Sensitivity is the proportion of High(positive) among cancer patients. Specificity is the proportion of low(negative) among benign tumors. Accuracy is the proportion of correctly diagnosed among analyzed patients. Area under the curve(AUC) is the area under the ROC curve, which is the plot of sensitivity by 1-specificity.
    Time Frame Up to 2 years

    Outcome Measure Data

    Analysis Population Description
    Patients analyzed among enrolled patients
    Arm/Group Title Diagnostic (18F-FDG PET/CT, 18F-FSPG PET/CT)
    Arm/Group Description Patients undergo 18F-FDG PET/CT scan per standard of care. Within 15 working days, patients also undergo 18F-FSPG PET scan over 60 minutes followed by an 18F-FSPG PET/CT scan over 30 minutes. Computed Tomography: Undergo 18F-FDG PET/CT - standard of care Computed Tomography: Undergo 18F-FSPG PET/CT fluorodeoxyglucose F-18: Undergo 18F-FDG PET/CT - standard of care Fluorine F 18 L-glutamate Derivative BAY94-9392: Undergo 18F-FSPG PET/CT Laboratory Biomarker Analysis: Correlative studies Positron Emission Tomography: Undergo 18F-FDG PET/CT - standard of care Positron Emission Tomography (PET): Undergo 18F-FSPG PET/CT
    Measure Participants 26
    FDG sensitivity(low and high)
    0.706
    FDG specificity
    0.778
    FDG accuracy
    0.731
    FDG AUC(area under curve)
    0.817
    ESPG sensitivity(low and high)
    0.824
    ESPG specificity(low and high)
    0.667
    ESPG accuracy
    0.769
    ESPG AUC
    0.843
    2. Secondary Outcome
    Title CD44 and xC- Expression Levels in Tissue Samples(0-3)
    Description The level of expression of xCT and CD44 proteins in the cytoplasmic membrane of tumor cells were examined by an experienced pathologist who was blinded to any patient and imaging information. The percentage of tumor cells positive for the marker and the intensity of staining were evaluated, the latter using a scale of 0 (none), 1+ (weak), 2+ (intermediate), and 3+ (strong) with a sample being reported as positive if greater than 10% of the tumor cells in the sample were positively stained with any intensity.
    Time Frame Up to 2 years

    Outcome Measure Data

    Analysis Population Description
    12 cancer patients among those enrolled.
    Arm/Group Title Some Cancer Patients
    Arm/Group Description Patients undergo 18F-FDG PET/CT scan per standard of care. Within 15 working days, patients also undergo 18F-FSPG PET scan over 60 minutes followed by an 18F-FSPG PET/CT scan over 30 minutes. Computed Tomography: Undergo 18F-FDG PET/CT - standard of care Computed Tomography: Undergo 18F-FSPG PET/CT fluorodeoxyglucose F-18: Undergo 18F-FDG PET/CT - standard of care Fluorine F 18 L-glutamate Derivative BAY94-9392: Undergo 18F-FSPG PET/CT Laboratory Biomarker Analysis: Correlative studies Positron Emission Tomography: Undergo 18F-FDG PET/CT - standard of care Positron Emission Tomography (PET): Undergo 18F-FSPG PET/CT
    Measure Participants 12
    CD44
    2.6
    (0.5)
    xCT
    1
    (1)
    3. Secondary Outcome
    Title Uptake of 18F-FSPG (Expressed in Maximal Standardized Uptake Value [SUV] Within the Tumor)
    Description Maximum standardized uptake values (SUVmax) were normalized to lean body mass and measured with a 1 cm diameter round region of interest over the area of greatest uptake in the lesion being measured.
    Time Frame Up to 2 years

    Outcome Measure Data

    Analysis Population Description
    enrolled patients included 7 benign and 19 cancer patients.
    Arm/Group Title Benign Patients Cancer Patients
    Arm/Group Description Patients undergo 18F-FDG PET/CT scan per standard of care. Within 15 working days, patients also undergo 18F-FSPG PET scan over 60 minutes followed by an 18F-FSPG PET/CT scan over 30 minutes. Computed Tomography: Undergo 18F-FDG PET/CT - standard of care Computed Tomography: Undergo 18F-FSPG PET/CT fluorodeoxyglucose F-18: Undergo 18F-FDG PET/CT - standard of care Fluorine F 18 L-glutamate Derivative BAY94-9392: Undergo 18F-FSPG PET/CT Laboratory Biomarker Analysis: Correlative studies Positron Emission Tomography: Undergo 18F-FDG PET/CT - standard of care Positron Emission Tomography (PET): Undergo 18F-FSPG PET/CT Patients undergo 18F-FDG PET/CT scan per standard of care. Within 15 working days, patients also undergo 18F-FSPG PET scan over 60 minutes followed by an 18F-FSPG PET/CT scan over 30 minutes. Computed Tomography: Undergo 18F-FDG PET/CT - standard of care Computed Tomography: Undergo 18F-FSPG PET/CT fluorodeoxyglucose F-18: Undergo 18F-FDG PET/CT - standard of care Fluorine F 18 L-glutamate Derivative BAY94-9392: Undergo 18F-FSPG PET/CT
    Measure Participants 9 17
    Mean (Standard Deviation) [Maximum standardized uptake values (SUVm]
    0.8
    (0.7)
    3.9
    (3.6)
    4. Secondary Outcome
    Title Ability of 18F-FSPG PET/CT to Stage of Lung Cancer (Metastatic or Not)
    Description Sensitivity, specificity, overall accuracy and ROC curves will be generated and compared for both 18F-FDG and 18F-FSPG tests. Wilcoxon rank-sum or Kruskal-Wallis tests will be applied for the group comparisons of the biodistribution characteristics of 18F-FDG and 18F-FSPG tests. Sensitivity is the proportion of High(positive) among cancer patients. Specificity is the proportion of low(negative) among benign tumors. Accuracy is the proportion of correctly diagnosed among all patients. Area under the curve(AUC) is the area under the ROC curve.
    Time Frame Up to 2 years

    Outcome Measure Data

    Analysis Population Description
    Cancer patients enrolled.
    Arm/Group Title Diagnostic (18F-FDG PET/CT, 18F-FSPG PET/CT)
    Arm/Group Description Patients undergo 18F-FDG PET/CT scan per standard of care. Within 15 working days, patients also undergo 18F-FSPG PET scan over 60 minutes followed by an 18F-FSPG PET/CT scan over 30 minutes. Computed Tomography: Undergo 18F-FDG PET/CT - standard of care Computed Tomography: Undergo 18F-FSPG PET/CT fluorodeoxyglucose F-18: Undergo 18F-FDG PET/CT - standard of care Fluorine F 18 L-glutamate Derivative BAY94-9392: Undergo 18F-FSPG PET/CT Laboratory Biomarker Analysis: Correlative studies Positron Emission Tomography: Undergo 18F-FDG PET/CT - standard of care Positron Emission Tomography (PET): Undergo 18F-FSPG PET/CT
    Measure Participants 17
    FDG sensitivity
    0.8
    FDG specificity
    0.857
    FDG accuracy
    0.824
    FDG AUC
    0.871
    FSPG sensitivity
    0.2
    FSPG specificity
    0.286
    FSPG accuracy
    0.235
    FSPG AUC
    0.8
    5. Other Pre-specified Outcome
    Title Uptake of 18F-FSPG (Expressed in Maximal Standardized Uptake Value [SUV] Within the
    Description Descriptive statistics, including means, standard deviations, and ranges for continuous
    Time Frame Up to 2 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description

    Adverse Events

    Time Frame From study entry to approximately 60 days
    Adverse Event Reporting Description
    Arm/Group Title Diagnostic (18F-FDG PET/CT, 18F-FSPG PET/CT)
    Arm/Group Description Patients undergo 18F-FDG PET/CT scan per standard of care. Within 15 working days, patients also undergo 18F-FSPG PET scan over 60 minutes followed by an 18F-FSPG PET/CT scan over 30 minutes. Computed Tomography: Undergo 18F-FDG PET/CT - standard of care Computed Tomography: Undergo 18F-FSPG PET/CT fluorodeoxyglucose F-18: Undergo 18F-FDG PET/CT - standard of care Fluorine F 18 L-glutamate Derivative BAY94-9392: Undergo 18F-FSPG PET/CT Laboratory Biomarker Analysis: Correlative studies Positron Emission Tomography: Undergo 18F-FDG PET/CT - standard of care Positron Emission Tomography (PET): Undergo 18F-FSPG PET/CT
    All Cause Mortality
    Diagnostic (18F-FDG PET/CT, 18F-FSPG PET/CT)
    Affected / at Risk (%) # Events
    Total 6/46 (13%)
    Serious Adverse Events
    Diagnostic (18F-FDG PET/CT, 18F-FSPG PET/CT)
    Affected / at Risk (%) # Events
    Total 1/46 (2.2%)
    Respiratory, thoracic and mediastinal disorders
    Pneumothorax 1/46 (2.2%) 1
    Other (Not Including Serious) Adverse Events
    Diagnostic (18F-FDG PET/CT, 18F-FSPG PET/CT)
    Affected / at Risk (%) # Events
    Total 7/46 (15.2%)
    General disorders
    Non-cardiac chest pain 4/46 (8.7%) 5
    Respiratory, thoracic and mediastinal disorders
    Dyspnea 4/46 (8.7%) 4

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Teresa Melton
    Organization Vanderbilt-Ingram Cancer Center
    Phone 615-936-7423
    Email teresa.melton@vumc.org
    Responsible Party:
    Chirayu Shah, Associate Professor of Clinical Radiology, Vanderbilt-Ingram Cancer Center
    ClinicalTrials.gov Identifier:
    NCT02448225
    Other Study ID Numbers:
    • VICC THO 1524
    • NCI-2015-00748
    • P30CA068485
    First Posted:
    May 19, 2015
    Last Update Posted:
    Aug 1, 2022
    Last Verified:
    Jul 1, 2022