Cigarette Smoking Behavior, Lung Carcinoma, Solitary Pulmonary Nodule
Conditions
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.
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.
Interventions
PROCEDUREComputed Tomography
Undergo 18F-FDG PET/CT - standard of care
RADIATIONfluorodeoxyglucose F-18
Undergo 18F-FDG PET/CT - standard of care
Undergo 18F-FSPG PET/CT
OTHERLaboratory Biomarker Analysis
Correlative studies
PROCEDUREPositron Emission Tomography
Undergo 18F-FDG PET/CT - standard of care
PROCEDUREPositron Emission Tomography (PET)
Undergo 18F-FSPG PET/CT
Sponsors
National Cancer Institute (NCI)
Vanderbilt-Ingram Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
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.
Participants by arm
| Arm | Count |
|---|---|
| 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.
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 | 46 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Did not get FSPG scan | 18 |
| Overall Study | Treated between the FDG and FSPG scan | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Diagnostic (18F-FDG PET/CT, 18F-FSPG PET/CT) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 23 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 43 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 40 Participants |
| Region of Enrollment United States | 46 participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 6 / 46 |
| other Total, other adverse events | 7 / 46 |
| serious Total, serious adverse events | 1 / 46 |
Outcome results
Primary
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.
Time frame: Up to 2 years
Population: Patients analyzed among enrolled patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Diagnostic (18F-FDG PET/CT, 18F-FSPG PET/CT) | Ability of 18F-FSPG PET/CT to Discriminate Benign From Malignant Nodules | FDG accuracy | 0.731 proportion, range 0 to 1, higher better |
| Diagnostic (18F-FDG PET/CT, 18F-FSPG PET/CT) | Ability of 18F-FSPG PET/CT to Discriminate Benign From Malignant Nodules | ESPG accuracy | 0.769 proportion, range 0 to 1, higher better |
| Diagnostic (18F-FDG PET/CT, 18F-FSPG PET/CT) | Ability of 18F-FSPG PET/CT to Discriminate Benign From Malignant Nodules | FDG sensitivity(low and high) | 0.706 proportion, range 0 to 1, higher better |
| Diagnostic (18F-FDG PET/CT, 18F-FSPG PET/CT) | Ability of 18F-FSPG PET/CT to Discriminate Benign From Malignant Nodules | FDG specificity | 0.778 proportion, range 0 to 1, higher better |
| Diagnostic (18F-FDG PET/CT, 18F-FSPG PET/CT) | Ability of 18F-FSPG PET/CT to Discriminate Benign From Malignant Nodules | FDG AUC(area under curve) | 0.817 proportion, range 0 to 1, higher better |
| Diagnostic (18F-FDG PET/CT, 18F-FSPG PET/CT) | Ability of 18F-FSPG PET/CT to Discriminate Benign From Malignant Nodules | ESPG sensitivity(low and high) | 0.824 proportion, range 0 to 1, higher better |
| Diagnostic (18F-FDG PET/CT, 18F-FSPG PET/CT) | Ability of 18F-FSPG PET/CT to Discriminate Benign From Malignant Nodules | ESPG specificity(low and high) | 0.667 proportion, range 0 to 1, higher better |
| Diagnostic (18F-FDG PET/CT, 18F-FSPG PET/CT) | Ability of 18F-FSPG PET/CT to Discriminate Benign From Malignant Nodules | ESPG AUC | 0.843 proportion, range 0 to 1, higher better |
Secondary
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.
Time frame: Up to 2 years
Population: Cancer patients enrolled.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Diagnostic (18F-FDG PET/CT, 18F-FSPG PET/CT) | Ability of 18F-FSPG PET/CT to Stage of Lung Cancer (Metastatic or Not) | FDG sensitivity | 0.8 proportion, range 0-1, higher better |
| Diagnostic (18F-FDG PET/CT, 18F-FSPG PET/CT) | Ability of 18F-FSPG PET/CT to Stage of Lung Cancer (Metastatic or Not) | FDG specificity | 0.857 proportion, range 0-1, higher better |
| Diagnostic (18F-FDG PET/CT, 18F-FSPG PET/CT) | Ability of 18F-FSPG PET/CT to Stage of Lung Cancer (Metastatic or Not) | FDG accuracy | 0.824 proportion, range 0-1, higher better |
| Diagnostic (18F-FDG PET/CT, 18F-FSPG PET/CT) | Ability of 18F-FSPG PET/CT to Stage of Lung Cancer (Metastatic or Not) | FDG AUC | 0.871 proportion, range 0-1, higher better |
| Diagnostic (18F-FDG PET/CT, 18F-FSPG PET/CT) | Ability of 18F-FSPG PET/CT to Stage of Lung Cancer (Metastatic or Not) | FSPG sensitivity | 0.2 proportion, range 0-1, higher better |
| Diagnostic (18F-FDG PET/CT, 18F-FSPG PET/CT) | Ability of 18F-FSPG PET/CT to Stage of Lung Cancer (Metastatic or Not) | FSPG specificity | 0.286 proportion, range 0-1, higher better |
| Diagnostic (18F-FDG PET/CT, 18F-FSPG PET/CT) | Ability of 18F-FSPG PET/CT to Stage of Lung Cancer (Metastatic or Not) | FSPG accuracy | 0.235 proportion, range 0-1, higher better |
| Diagnostic (18F-FDG PET/CT, 18F-FSPG PET/CT) | Ability of 18F-FSPG PET/CT to Stage of Lung Cancer (Metastatic or Not) | FSPG AUC | 0.8 proportion, range 0-1, higher better |
Secondary
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.
Time frame: Up to 2 years
Population: 12 cancer patients among those enrolled.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Diagnostic (18F-FDG PET/CT, 18F-FSPG PET/CT) | CD44 and xC- Expression Levels in Tissue Samples(0-3) | CD44 | 2.6 IHC score, range 0 and above | Standard Deviation 0.5 |
| Diagnostic (18F-FDG PET/CT, 18F-FSPG PET/CT) | CD44 and xC- Expression Levels in Tissue Samples(0-3) | xCT | 1 IHC score, range 0 and above | Standard Deviation 1 |
Secondary
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.
Time frame: Up to 2 years
Population: enrolled patients included 7 benign and 19 cancer patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diagnostic (18F-FDG PET/CT, 18F-FSPG PET/CT) | Uptake of 18F-FSPG (Expressed in Maximal Standardized Uptake Value [SUV] Within the Tumor) | 0.8 Maximum standardized uptake values (SUVm | Standard Deviation 0.7 |
| Cancer Patients | Uptake of 18F-FSPG (Expressed in Maximal Standardized Uptake Value [SUV] Within the Tumor) | 3.9 Maximum standardized uptake values (SUVm | Standard Deviation 3.6 |
Other Pre-specified
Uptake of 18F-FSPG (Expressed in Maximal Standardized Uptake Value [SUV] Within the
Descriptive statistics, including means, standard deviations, and ranges for continuous
Time frame: Up to 2 years