Intracranial Neoplasm, Low Grade Glioma, Recurrent Glioblastoma, Recurrent WHO Grade III Glioma, Recurrent World Health Organization (WHO) Grade II Glioma
Conditions
Brief summary
This phase II trial studies how well F-18 fluoroethyltyrosine (fluoroethyltyrosine) works in detecting tumors in participants with intracranial tumors that have come back. FET accumulates in malignant cells within intracranial neoplasms and can be used to detect recurrent disease and characterize the grade of glial neoplasms. Imaging agents such as FET can help oncologist to see the tumor better during a positron emission tomography (PET) scan.
Detailed description
PRIMARY OBJECTIVES: I. To determine if FET PET can differentiate between benign treatment-related changes (TRC) and recurrent glioma in comparison to a composite standard of truth (CSOT) that includes pathology and other clinical information, evaluated using estimates of sensitivity and specificity (Combined populations) SECONDARY OBJECTIVES: I. To determine if FET PET can differentiate between benign TRC and recurrent glioma in comparison to a histopathological standard of truth.(Combined populations). II. To determine if FET PET can differentiate between benign TRC and recurrent glioma in comparison to a CSOT evaluated using estimates other than subject-based sensitivity and specificity.(Combined populations). III. To assess the safety of FET PET, as determined by treatment emergent adverse events (TEAEs) within 48 hours of FET administration.(Combined populations). IV. To describe the inter-reader variability between 3 independent blinded readers of FET PET images in assessments of benign TRC versus recurrent glioma.(Combined populations). V. To describe intra-reader variability between 3 independent blinded readers of FET PET images in the assessments of benign TRC versus recurrent glioma.(Combined populations). EXPLORATORY OBJECTIVES: I. To assess relationships between serial FET PET and clinical outcome (benign TRC and recurrence) in patients with recurrent metastatic lesions, recurrent high grade gliomas and recurrent low-grade gliomas. II. To determine if MRI can differentiate between benign treatment-related changes and recurrence. III. To describe the distribution of the standardized uptake value (SUV) and tumor-to-background ratio (TBR) for observed lesions. IV. To determine if FET PET can differentiate between benign TRC and recurrent metastatic lesions. V. To determine if FET PET can accurately differentiate between low-grade and high-grade gliomas (Population 2). OUTLINE: Participants receive F-18 fluoroethyltyrosine intravenously (IV) over approximately 1 minute and undergo PET over 40 minutes. After completion of study treatment, participants are followed up periodically.
Interventions
DRUGF-18 Fluoroethyltyrosine (FET)
Patients given an injected dose of 4 to 7 millicurie (mCi) of FET per scan. The radiopharmaceutical will be administered while the patient is in the PET scanner
PROCEDUREPositron Emission Tomography (PET)
All patients receive single PET imaging lasting for 40 minutes. Acquired PET data will be reconstructed so that three time points are created: (1) Perfusion: 60-second acquisition that starts immediately when activity is noted in the field of view, (2) Equilibrium: 10-minute acquisition acquired between 10 and 20 minutes after injection, and (3) Washout: 10-minute acquisition acquired between 30 and 40 minutes after injection. A repeat PET image will be offered to adult patients.
Sponsors
Thomas Hope
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \> 3 years. * Presence or suspicion of intracranial neoplasm in two populations. * Population 1: Patients after primary treatment (radiation therapy and/or surgery) with suspicion of recurrence on magnetic resonance imaging (MRI). Three sub-populations will be considered: * Recurrent metastatic lesions. * Recurrent high-grade gliomas (grades 3 and 4). * Recurrent low-grade gliomas (grades 1 and 2). * Population 2: Patients prior to primary treatment with planned biopsy or surgical resection.
Exclusion criteria
* Patient with known incompatibility to PET or computed tomography (CT)/MRI scans. * Patient unlikely to comply with study procedures, restrictions and requirements and judged by the investigator to be unsuitable for study participation. * Sedation or anesthesia can be used for patients who cannot tolerate the exam.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity of Fluoroethyltyrosine (FET) PET using a composite standard of truth (CSOT) (subject-level) | Up to 6 months | Sensitivity is defined as a percentage of all participants with a true positive (TP) FET PET scan result relative to participants with a positive CSOT result = \[TP / (TP + FN)\] x 100. The CSOT for recurrence or benign treatment-related changes (TRC) will be evaluated by a panel of physicians independent of FET images and determined based on histopathology and other clinical data. Histopathology of target lesions obtained may be reviewed for up to 6 months after imaging. Positive for recurrence on follow-up scans will be based on Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. For lesion-level standards, features of RANO will be considered. Histopathology and imaging will be primary factors used in determinations, followed by additional clinical data. From this, an overall determination will be made for each individual lesion, and this will be considered together with the patient-level determination. |
| Specificity of FET PET using a CSOT (subject-level) | Up to 6 months | Specificity is defined as percentage of all participants with a true negative (TN) FET PET scan result relative to participants with a negative CSOT result = \[TN / (TN + FP)\] x 100. The CSOT for recurrence or benign treatment-related changes (TRC) will be evaluated by a panel of physicians independent of FET images and determined based on histopathology and other clinical data. Histopathology of target lesions obtained may be reviewed for up to 6 months after imaging. Positive for recurrence on follow-up scans will be based on Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. For lesion-level standards, features of RANO will be considered. Histopathology and imaging will be primary factors used in determinations, followed by additional clinical data. From this, an overall determination will be made for each individual lesion, and this will be considered together with the patient-level determination. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity of FET PET using a histopathology standard of truth (lesion-level) | Up to 6 months | Sensitivity is defined as percentage of all lesions with a true positive (TP) FET PET scan result relative to all lesions with a positive histological result = \[TP / (TP + FN)\] x 100. For cases with available histopathology, the histopathology standard of truth for recurrence (positive) or TRC (negative) will also be determined by the Truth Panel as an intermediate result while reviewing histopathology as part of their overall assessment of each lesion. |
| Specificity of FET PET using a histopathology standard of truth (subject-level) | Up to 6 months | Specificity is defined as percentage of all participants with a true negative (TN) FET PET scan result relative to all participants with a negative histological result = \[TN / (TN + FP)\] x 100. For cases with available histopathology, the histopathology standard of truth for recurrence (positive) or TRC (negative) will also be determined by the Truth Panel as an intermediate result while reviewing histopathology as part of their overall assessment of each subject. |
| Specificity of FET PET using a histopathology standard of truth (lesion-level) | Up to 6 months | Specificity is defined as percentage of all lesions with a true negative (TN) scan result relative to all lesions with a negative histological result = \[TN / (TN + FP)\] x 100. For cases with available histopathology, the histopathology standard of truth for recurrence (positive) or TRC (negative) will also be determined by the Truth Panel as an intermediate result while reviewing histopathology as part of their overall assessment of each lesion. |
| Positive Predictive Value (PPV) using a histopathology standard of truth (subject-level) | Up to 6 months | The positive predictive value for all participants is defined as the probability that a positive histological standard of truth result is obtained given that the result of the FET PET scan is positive and reported as a percentage across all participants = \[TP / (TP + FP)\] x 100. For cases with available histopathology, the histopathology standard of truth for recurrence (positive) or TRC (negative) will also be determined by the Truth Panel as an intermediate result while reviewing histopathology as part of their overall assessment of each subject. |
| Positive Predictive Value (PPV) using a histopathology standard of truth (lesion-level) | Up to 6 months | The positive predictive value for all lesions is defined as the probability that a positive histological standard of truth result is obtained given that the result of the FET PET scan is positive and reported as a percentage of all lesions = \[TP / (TP + FP)\] x 100. For cases with available histopathology, the histopathology standard of truth for recurrence (positive) or TRC (negative) will also be determined by the Truth Panel as an intermediate result while reviewing histopathology as part of their overall assessment of each lesion. |
| Negative Predictive Value (NPV) using a histopathology standard of truth (subject-level) | Up to 6 months | The negative predictive value for all participants is defined as the probability that a negative standard of truth result is obtained given that the result of the FET PET scan is negative and reported as a percentage of all participants = \[TN / (TN + FN)\] x 100. For cases with available histopathology, the histopathology standard of truth for recurrence (positive) or TRC (negative) will also be determined by the Truth Panel as an intermediate result while reviewing histopathology as part of their overall assessment of each subject. |
| Negative Predictive Value (NPV) using a histopathology standard of truth (lesion-level) | Up to 6 months | The negative predictive value for all lesions is defined as the probability that a negative standard of truth result is obtained given that the result of the FET PET scan is negative and reported as a percentage of all lesions = \[TN / (TN + FN)\] x 100. For cases with available histopathology, the histopathology standard of truth for recurrence (positive) or TRC (negative) will also be determined by the Truth Panel as an intermediate result while reviewing histopathology as part of their overall assessment of each lesion. |
| Accuracy of FET PET using a histopathology standard of truth (subject-level) | Up to 6 months | The accuracy is defined as the probability that the FET PET scan result for all participants is correct using histopathological results and reported as a percentage: Accuracy (%) = \[(TP + TN) / (TP + FP + TN + FN)\] x 100. For cases with available histopathology, the histopathology standard of truth for recurrence (positive) or TRC (negative) will also be determined by the Truth Panel as an intermediate result while reviewing histopathology as part of their overall assessment of each subject. |
| Accuracy of FET PET using a histopathology standard of truth (lesion-level) | Up to 6 months | The accuracy is defined as the probability that the FET PET scan result for all lesions is correct using histopathological results and reported as a percentage: Accuracy (%) = \[(TP + TN) / (TP + FP + TN + FN)\] x 100. For cases with available histopathology, the histopathology standard of truth for recurrence (positive) or TRC (negative) will also be determined by the Truth Panel as an intermediate result while reviewing histopathology as part of their overall assessment of each lesion. |
| Misclassification rate for FET PET using a histopathology standard of truth (Subject-level) | Up to 6 months | The misclassification rate is defined as the probability that the FET PET scan result for all participants is not correct using histopathological results and reported as a percentage: Misclassification Rate (%) = \[(FP + FN) / (TP + FP + TN + FN)\] x 100. For cases with available histopathology, the histopathology standard of truth for recurrence (positive) or TRC (negative) will also be determined by the Truth Panel as an intermediate result while reviewing histopathology as part of their overall assessment of each subject. |
| Misclassification rate for FET PET using a histopathology standard of truth (lesion-level) | Up to 6 months | The misclassification rate is defined as the probability that the FET PET scan result for all lesions is not correct using histopathological results and reported as a percentage: Misclassification Rate (%) = \[(FP + FN) / (TP + FP + TN + FN)\] x 100. For cases with available histopathology, the histopathology standard of truth for recurrence (positive) or TRC (negative) will also be determined by the Truth Panel as an intermediate result while reviewing histopathology as part of their overall assessment of each lesion. |
| Sensitivity of FET PET using a CSOT (lesion-level) | Up to 6 months | Sensitivity is defined as a percentage of all lesions with a true positive (TP) FET PET scan result relative to lesions with a positive CSOT result = \[TP / (TP + FN)\] x 100. The CSOT for recurrence or benign treatment-related changes (TRC) will be evaluated by a panel of physicians independent of FET images and determined based on histopathology and other clinical data. Histopathology of target lesions obtained may be reviewed for up to 6 months after imaging. Positive for recurrence on follow-up scans will be based on Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. For lesion-level standards, features of RANO will be considered. Histopathology and imaging will be primary factors used in determinations, followed by additional clinical data. From this, an overall determination will be made for each individual lesion. |
| Specificity of FET PET using a CSOT (lesion-level) | Up to 6 months | Specificity is defined as percentage of all lesions with a true negative (TN) FET PET scan result relative to lesions with a negative CSOT result = \[TN / (TN + FP)\] x 100. The CSOT for recurrence or benign treatment-related changes (TRC) will be evaluated by a panel of physicians independent of FET images and determined based on histopathology and other clinical data. Histopathology of target lesions obtained may be reviewed for up to 6 months after imaging. Positive for recurrence on follow-up scans will be based on Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. For lesion-level standards, features of RANO will be considered. Histopathology and imaging will be primary factors used in determinations, followed by additional clinical data. From this, an overall determination will be made for each individual lesion. |
| PPV of FET PET using a CSOT (subject-level) | Up to 6 months | The positive predictive value is defined as the probability that a positive CSOT result is obtained given that the result of the FET PET scan is positive, PPV (%) = \[TP / (TP + FP)\] x 100. The CSOT for recurrence or benign treatment-related changes (TRC) will be evaluated by a panel of physicians independent of FET images and determined based on histopathology and other clinical data. Histopathology of target lesions obtained may be reviewed for up to 6 months after imaging. Positive for recurrence on follow-up scans will be based on Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. For lesion-level standards, features of RANO will be considered. Histopathology and imaging will be primary factors used in determinations, followed by additional clinical data. From this, an overall determination will be made for each individual lesion, and this will be considered together with the patient-level determination. |
| PPV of FET PET using a CSOT (lesion-level) | Up to 6 months | The positive predictive value is defined as the probability that a CSOT result is obtained given that the result of the FET PET scan is positive PPV (%) = \[TP / (TP + FP)\] x 100. The CSOT for recurrence or benign treatment-related changes (TRC) will be evaluated by a panel of physicians independent of FET images and determined based on histopathology and other clinical data. Histopathology of target lesions obtained may be reviewed for up to 6 months after imaging. Positive for recurrence on follow-up scans will be based on Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. For lesion-level standards, features of RANO will be considered. Histopathology and imaging will be primary factors used in determinations, followed by additional clinical data. From this, an overall determination will be made for each individual lesion. |
| NPV of FET PET using a CSOT (subject-level) | Up to 6 months | The negative predictive value is defined as the probability that a negative CSOT result is obtained given that the result of the FET PET scan is negative, NPV (%) = \[TN / (TN + FN)\] x 100. The CSOT for recurrence or benign treatment-related changes (TRC) will be evaluated by a panel of physicians independent of FET images and determined based on histopathology and other clinical data. Histopathology of target lesions obtained may be reviewed for up to 6 months after imaging. Positive for recurrence on follow-up scans will be based on Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. For lesion-level standards, features of RANO will be considered. Histopathology and imaging will be primary factors used in determinations, followed by additional clinical data. From this, an overall determination will be made for each individual lesion, and this will be considered together with the patient-level determination. |
| NPV of FET PET using a CSOT (lesion-level) | Up to 6 months | The negative predictive value is defined as the probability that a negative CSOT result is obtained given that the result of the FET PET scan is negative, NPV (%) = \[TN / (TN + FN)\] x 100. The CSOT for recurrence or benign treatment-related changes (TRC) will be evaluated by a panel of physicians independent of FET images and determined based on histopathology and other clinical data. Histopathology of target lesions obtained may be reviewed for up to 6 months after imaging. Positive for recurrence on follow-up scans will be based on Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. For lesion-level standards, features of RANO will be considered. Histopathology and imaging will be primary factors used in determinations, followed by additional clinical data. From this, an overall determination will be made for each individual lesion. |
| Accuracy of FET PET using a CSOT (subject-level) | Up to 6 months | The accuracy is defined as the probability that the FET PET scan result is correct, Accuracy (%) = \[(TP + TN) / (TP + FP + TN + FN)\] x 100. The CSOT for recurrence or benign treatment-related changes (TRC) will be evaluated by a panel of physicians independent of FET images and determined based on histopathology and other clinical data. Histopathology of target lesions obtained may be reviewed for up to 6 months after imaging. Positive for recurrence on follow-up scans will be based on Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. For lesion-level standards, features of RANO will be considered. Histopathology and imaging will be primary factors used in determinations, followed by additional clinical data. From this, an overall determination will be made for each individual lesion, and this will be considered together with the patient-level determination. |
| Accuracy of FET PET using a CSOT (lesion-level) | Up to 6 months | The accuracy is defined as the probability that the FET PET scan result is correct, Accuracy (%) = \[(TP + TN) / (TP + FP + TN + FN)\] x 100. The CSOT for recurrence or benign treatment-related changes (TRC) will be evaluated by a panel of physicians independent of FET images and determined based on histopathology and other clinical data. Histopathology of target lesions obtained may be reviewed for up to 6 months after imaging. Positive for recurrence on follow-up scans will be based on Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. For lesion-level standards, features of RANO will be considered. Histopathology and imaging will be primary factors used in determinations, followed by additional clinical data. From this, an overall determination will be made for each individual lesion. |
| Misclassification rate for FET PET using CSOT (subject-level) | Up to 6 months | The misclassification rate is defined as the probability that the FET PET scan result is not correct, Misclassification Rate (%) = \[(FP + FN) / (TP + FP + TN + FN)\] x 100. The CSOT for recurrence or benign treatment-related changes (TRC) will be evaluated by a panel of physicians independent of FET images and determined based on histopathology and other clinical data. Histopathology of target lesions obtained may be reviewed for up to 6 months after imaging. Positive for recurrence on follow-up scans will be based on Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. For lesion-level standards, features of RANO will be considered. Histopathology and imaging will be primary factors used in determinations, followed by additional clinical data. From this, an overall determination will be made for each individual lesion, and this will be considered together with the patient-level determination. |
| Misclassification rate for FET PET using CSOT (lesion-level) | Up to 6 months | The misclassification rate is defined as the probability that the FET PET scan result is not correct, Misclassification Rate (%) = \[(FP + FN) / (TP + FP + TN + FN)\] x 100. The CSOT for recurrence or benign treatment-related changes (TRC) will be evaluated by a panel of physicians independent of FET images and determined based on histopathology and other clinical data. Histopathology of target lesions obtained may be reviewed for up to 6 months after imaging. Positive for recurrence on follow-up scans will be based on Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. For lesion-level standards, features of RANO will be considered. Histopathology and imaging will be primary factors used in determinations, followed by additional clinical data. From this, an overall determination will be made for each individual lesion. |
| Degree of inter-rater reliability | Up to 6 months | Inter-reader variability will be analyzed using Fleiss' kappa statistic to determine the agreement between three independent blinded readers in assessing FET PET images as recurrence or TRC. Fleiss's kappa ranges from 0 to 1, where 0 indicates no agreement beyond chance, 1 indicates perfect agreement among all raters. |
| Proportion of all participants with reported treatment-emergent adverse events (TEAEs) | Up to 48 hours after FET PET imaging | The proportion of all participants who have reported grade 3 and above adverse events after receiving interventional scan will be recorded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) v.4 will be reported. |
| Reproducibility of inter-rater reliability | Up to 6 months | Intra-reader variability will be analyzed based on a random sample of 15 subjects whose images were re- reviewed by the same reader. The percent of agreement between the two interpretations will be computed for each reader. Cohen's kappa statistics will be used to determine the reproducibility of the assessment by individual readers when analyzing the same data repeatedly. Cohen's Kappa ranges from -1 to 1, where-1 indicates complete disagreement between raters, 0 indicates agreement no better than chance, 1 indicates complete agreement between raters. |
| Sensitivity of FET PET using a histopathology standard of truth (subject-level) | Up to 6 months | Sensitivity is defined as percentage of all participants with a true positive (TP) FET PET scan result relative to all participants with a positive histological result = \[TP / (TP + FN)\] x 100. For cases with available histopathology, the histopathology standard of truth for recurrence (positive) or TRC (negative) will also be determined by the Truth Panel as an intermediate result while reviewing histopathology as part of their overall assessment of each subject. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORThomas A Hope, MD
University of California, San Francisco
Outcome results
None listed