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

PET Imaging of Lung Cancer and Indeterminate Pulmonary Nodules With 18F-FSPG

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.

Study Overview

• Status: Completed
• Conditions: Lung Carcinoma; Cigarette Smoking Behavior; Solitary Pulmonary Nodule
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Procedure: Computed Tomography; Procedure: Computed Tomography; Radiation: fluorodeoxyglucose F-18; Drug: Fluorine F 18 L-glutamate Derivative BAY94-9392; Procedure: Positron Emission Tomography; Procedure: Positron Emission Tomography (PET)

Detailed Description

PRIMARY OBJECTIVES:

I. To compare the imaging characteristics of 18F-FSPG PET/CT with standard-of-care, 18F-FDG PET/CT.

II. 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.

III. 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 Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt-Ingram Cancer Center
    • Nashville, Tennessee, United States, 37212
      • Tennessee Valley Health System Nashville

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

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 (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.

Other: Laboratory Biomarker Analysis; Correlative studies; Procedure: Computed Tomography; Undergo 18F-FDG PET/CT - standard of care; Other Names: CT; CAT; CAT Scan; Computerized Axial Tomography; Computerized Tomography; tomography; CT SCAN; Procedure: Computed Tomography; Undergo 18F-FSPG PET/CT; Other Names: CT; CAT; CAT Scan; Computerized Axial Tomography; Computerized Tomography; tomography; CT SCAN; 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; Procedure: Positron Emission Tomography; Undergo 18F-FDG PET/CT - standard of care; Other Names: Medical Imaging, Positron Emission Tomography; PET; Positron Emission Tomography Scan; proton magnetic resonance spectroscopic imaging; PET SCAN; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ability of 18F-FSPG PET/CT to Discriminate Benign From Malignant Nodules	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.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CD44 and xC- Expression Levels in Tissue Samples(0-3)	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.	Up to 2 years
Uptake of 18F-FSPG (Expressed in Maximal Standardized Uptake Value [SUV] Within the Tumor)	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.	Up to 2 years
Ability of 18F-FSPG PET/CT to Stage of Lung Cancer (Metastatic or Not)	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.	Up to 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Uptake of 18F-FSPG (Expressed in Maximal Standardized Uptake Value [SUV] Within the	Descriptive statistics, including means, standard deviations, and ranges for continuous	Up to 2 years

Collaborators and Investigators

• Sponsor: Vanderbilt-Ingram Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Chirayu Shah, MD, Vanderbilt-Ingram Cancer Center

Publications and helpful links

Helpful Links

• Vanderbilt-Ingram Cancer Center, Find a Clinical Trial

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2015
• Primary Completion (Actual): August 2, 2021
• Study Completion (Actual): October 10, 2022

Study Registration Dates

• First Submitted: May 15, 2015
• First Submitted That Met QC Criteria: May 15, 2015
• First Posted (Estimate): May 19, 2015

Study Record Updates

• Last Update Posted (Actual): October 19, 2022
• Last Update Submitted That Met QC Criteria: October 17, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Multiple Pulmonary Nodules; Solitary Pulmonary Nodule; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Protective Agents; Radiopharmaceuticals; Cariostatic Agents; Fluorodeoxyglucose F18; Fluorides; Deoxyglucose
• Other Study ID Numbers: VICC THO 1524; P30CA068485 (U.S. NIH Grant/Contract); NCI-2015-00748 (Registry Identifier: CTRP (Clinical Trial Reporting Program))