18F-FSPG PET/CT in Diagnosing Early Lung Cancer in Patients With Lung Nodules

PRIMARY OBJECTIVES:

I. Comparison of fluorine F 18 L-glutamate derivative BAY94-9392 (18F-FSPG) accumulation with fludeoxyglucose F-18 (18F-FDG) accumulation to assess whether (4S)-4-(3-18F-Fluoropropyl)-L-Glutamate (18F-FSPG)-PET is better at discriminating between benign and malignant nodules.

SECONDARY OBJECTIVES:

I. To develop and validate early lung cancer detection biomarkers that would directly impact the growing need to integrate imaging and non-invasive molecular diagnostics for indeterminate pulmonary nodules and allow physicians to avoid unnecessary invasive procedures in patients with benign lung disease.

OUTLINE:

Patients receive 18F-FSPG intravenously (IV) and, undergo a PET/CT scan over 30-60 minutes. Within 24 hours-14 days, patients receive 18F-FDG and undergo a second PET/CT scan over 30-60 minutes.

After completion of study, patients are followed up within 24-72 hours.

• Computed Tomography (Diagnostic test), also known as CAT, CAT Scan, Computerized Axial Tomography, computerized tomography, CT, CT SCAN, tomography: Undergo PET/CT
• Fludeoxyglucose F-18 (Drug), also known as 18-FDG, FDG, fludeoxyglucose F 18, Fludeoxyglucose F18, Fluorine-18 2-Fluoro-2-deoxy-D-Glucose, Fluorodeoxyglucose F18: Given IV
• Fluorine F 18 L-glutamate Derivative BAY94-9392 (Drug), also known as (S)-4-(3-18F-fluoropropyl)-L-glutamic Acid, 18F-FSPG, BAY94-9392: Given IV
• Positron Emission Tomography (PET/CT) (Diagnostic test), also known as Positron Emission Tomography/computer tomography, CT Scan, PET Scan, Positron Emission Tomography, medical imaging: Undergo PET/CT

Primary outcomes

• Diagnostic Performance Metrics (Sensitivity, Specificity, PPV, NPV, and Accuracy) of Ultrasonography and Capnography for Malignant Lung Nodules [Through study completion, an average of 2 years and 6 months]: The diagnostic performance of ultrasonography and capnography in detecting malignant lung nodules was assessed using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy. Sensitivity and specificity were calculated to determine the ability to correctly identify malignant and non-malignant nodules, respectively. Results were compared to a predefined threshold of 75%, with all percentages reported as proportions of the total number of nodules analyzed. Confidence intervals were calculated for each metric to ensure precision and reliability in the estimates.

Secondary outcomes

• Improvement in Predictive Accuracy of Lung Nodule Diagnosis Using the C Statistic (Area Under the Curve, AUC) [Through study completion, an average of 2 years and 6 months]: The predictive accuracy of the lung nodule diagnosis model was assessed using the C statistic, also referred to as the area under the receiver operating characteristic (ROC) curve (AUC). Improved performance was defined as a statistically significant increase (p < 0.05) in the C statistic, determined using the DeLong test for comparing correlated ROC curves. The Mann-Whitney U test was also used to compare the distributions of the C statistic between diagnostic methods. Results are reported as the mean C statistic with 95% confidence intervals for each diagnostic method.

Sex: All, ages: 45 Years to any

Inclusion Criteria:

* Pulmonary nodule between the size of 7 to 30 mm. Subjects with multiple nodules may be eligible if the dominant nodule is 7 to 30 mm
* Undergoing standard of care 18F-FDG PET imaging (for indeterminate pulmonary nodule)
* Current or former cigarette smoker, with >= 20 pack years
* Documented informed consent

Exclusion Criteria:

* History or previous diagnosis of lung cancer
* Cancer diagnosis within the last 5 years
* Pregnant or nursing

Participant flow

Outcome results

• Diagnostic Performance Metrics (Sensitivity, Specificity, PPV, NPV, and Accuracy) of Ultrasonography and Capnography for Malignant Lung Nodules (Primary), Number, percentage: Diagnostic (18F-FSPG PET/CT) 100 (100 to 100); Diagnostic (18F-FDG PET/CT) 70 (35 to 93) (p 0.02)
• Improvement in Predictive Accuracy of Lung Nodule Diagnosis Using the C Statistic (Area Under the Curve, AUC) (Secondary), Mean, probability: Baseline Diagnostic (18F-FSPG PET/CT) 0.84 +/- 0.1; Improved Diagnostic (18F-FDG PET/CT) 1.0 +/- 0.0 (p 0.004)

Adverse events

Time frame: Within 24 to 72hours after the 18F-FSPG PET/CT

• Study Protocol and Statistical Analysis Plan (PDF, 2023-06-08)
• Informed Consent Form (PDF, 2023-10-24)

• Carina Mari Aparici, Principal investigator, Stanford Cancer Institute Palo Alto