18F-FSPG PET/CT in Imaging Patients With Newly Diagnosed Lung Cancer or Indeterminate Pulmonary Nodules
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 |
---|---|---|
|
Phase 2 |
Detailed Description
PRIMARY OBJECTIVES:
-
To compare the imaging characteristics of 18F-FSPG PET/CT with standard-of-care, 18F-FDG PET/CT.
-
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.
-
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
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:
Procedure: Computed Tomography
Undergo 18F-FSPG PET/CT
Other Names:
Radiation: fluorodeoxyglucose F-18
Undergo 18F-FDG PET/CT - standard of care
Other Names:
Drug: Fluorine F 18 L-glutamate Derivative BAY94-9392
Undergo 18F-FSPG PET/CT
Other Names:
Other: Laboratory Biomarker Analysis
Correlative studies
Procedure: Positron Emission Tomography
Undergo 18F-FDG PET/CT - standard of care
Other Names:
Procedure: Positron Emission Tomography (PET)
Undergo 18F-FSPG PET/CT
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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 Outcome Measures
- 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
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.- VICC THO 1524
- NCI-2015-00748
- P30CA068485
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
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
|
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)
|
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)
|
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
|
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
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 |
teresa.melton@vumc.org |
- VICC THO 1524
- NCI-2015-00748
- P30CA068485