Glioblastoma, Low Grade Glioma
Conditions
Brief summary
The goal of this clinical trial is to evaluate Positron emission tomography/computed tomography (PET/CT) imaging with the radiotracer 1-(2-\[18F\]fluoroethyl)-l-tryptophan (\[18F\]FETrp) in patients diagnosed with a glioma. This study has 3 aims: * to assess if the \[18F\]FETrp PET/CT can outperform Magnetic Resonance Imaging (MRI) by providing a better treatment target volume in newly diagnosed Stage 4 glioma patients * better differentiate tumor progression from radiation induced MRI changes in post treatment stage 4 gliomas * by giving a drug that can inhibit a pathway to allow objective assessment of treatment effects in low grade gliomas
Interventions
DRUGMinocycline 200mg/day
Minocycline 200mg orally daily to start within 14 days of the first \[18F\]FETrp PET/CT and taken until the second \[18F\]FETrp PET/CT obtained 25-44 days after the start of the Minocycline in Arm 3
DIAGNOSTIC_TEST[18F]FETrp PET/CT
\[18F\]FETrp PET/CT used in all three arms
Sponsors
Barbara Ann Karmanos Cancer Institute
Wayne State University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
FOR ARMS 1-3 Inclusion Criteria: * Age =18 years. * Patient is able to lie in the PET/CT scanner for at least 60 minutes while undergoing scanning. * Patient is willing and able to review, understand, and provide written consent for the study procedures and indicates that they are aware of the investigational nature of this study.
Exclusion criteria
* Patients who are pregnant or lactating are excluded. Premenopausal women (defined per institutional guidelines) must have a negative pregnancy test (urine or serum) within 7 days of the PET scan. * Severe increased intracranial pressure, status epilepticus, or other severe or progressing clinical symptoms requiring urgent intervention in the opinion of the treating * Karnofsky performance score \<60, as determined by one of the clinician co- investigators. ADDITIONAL CRITERIA FOR ARM 1: Inclusion Criteria: * Histopathology/cytopathological diagnosis of a glioblastoma without a history of radiation. * The tumor is deemed amenable for radiation treatment (pre-radiation planning MRI can be done before or after the PET scan). ADDITIONAL CRITERIA FOR ARM 2: Inclusion Criteria: * Previous histopathology/cytopathological diagnosis of glioblastoma. * History of glioma radiation. * Presence of a new or progressing enhancing brain lesion on follow-up clinical MRI suspicious for post-radiation glioma progression or late radiation-induced MRI changes (i.e., radiation injury), at least 7 mm in bidirectional diameter. * The most recent MRI, used for comparison with the PET/CT, is performed within 4 weeks of the planned PET scan. ADDITIONAL CRITERIA FOR ARM 3 Inclusion Criteria: * MRI diagnosis of a brain tumor, previously verified to be a low-grade (WHO grade 2, IDH (isocitrate dehydrogenase) mutant glioma, based on histopathology from biopsy or resection. * The detected mass on the most recent clinical MRI is at least 7 mm in bidirectional diameter (i.e., twice the PET scanner resolution). * The tumor does not require urgent (within 1 month) resection, steroid treatment, or radiation. * The most recent MRI, used for comparison with the PET/CT, is performed within 4 weeks. * Patient agrees to have a baseline and follow-up PET/CT scan (approximately 1 month later) and interval oral treatment with 200mg/day minocycline. * Due to planned minocycline treatment, patients will need to have adequate renal function
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference Between Dice Similarity Coefficients (DSC) of Position Emission Tomography (PET) High K Tumor Volume and DSC of MRI-based Tumor Volume (d-PETk-MRI) in Arm 1 | From the time of the pre-radiotherapy scans (Baseline) up to tumor progression or study completion, assessed at a maximum follow-up of 2 years. | A comparative evaluation of the predictive accuracy of pre-radiotherapy imaging modalities (V1) in forecasting the spatial location of future tumor progression (V2) defined by RANO (Response Assessment in Neuro-Oncology) 2.0 criteria. For each participant, two separate Dice Similarity Coefficients (DSC) will be calculated against the final progression volume (V2): one using the pre-radiotherapy PET High K influx map volume (V1\_PETk) and one using the structural MRI target volume (V1\_MRI). The primary endpoint (d-PETk-MRI) is the absolute difference calculated per patient as DSC\_PETk minus DSC\_MRI. The resulting continuous score ranges from -1 to +1. A positive score indicates that the novel kinetic PET parameter is a spatially superior predictor of subsequent localized tumor recurrence compared to standard clinical MRI planning fields. |
| Sensitivity of [18F]FETrp PET Kinetic Influx Rate (PETk) with a predefined L/C ratio threshold of 1.60 in differentiating Tumor Progression from Radiation Injury in Arm 2 | From the date of the [18F]FETrp PET/CT scan up to the date of confirmed ground truth designation via histopathology or serial MRI follow-up, assessed over a maximum period of 1 year per participant. | The diagnostic sensitivity of PETk post-radiation (T2) (PETk-T2) with a predefined L/C ratio threshold of 1.60 to correctly identify true glioblastoma progression. The true disease status (ground truth) is defined by follow-up serial MRIs using RANO 2.0 criteria or histopathologic evidence from surgical re-resection. Sensitivity is calculated as the proportion of true-positive tumor progression cases correctly identified by PETk out of all true-positive cases. |
| Change in [18F]FETrp Kinetic Influx Rate (K) Values Following One Month of Standard of Care Plus Indoleamine 2,3-dioxygenase (IDO) Inhibitor Treatment (d-PETK) in Arm 3 | From Baseline (within 2 weeks prior to treatment initiation) to 1-month post-treatment (30 days ± 5 days, up to 44 days). | The quantitative change in \[18F\]FETrp PET K values evaluated within the MRI-defined tumor mass from baseline to post treatment. The primary analysis will be performed on the per-protocol population, defined as participants who completed both pre- and post-treatment PET scans and demonstrated at least 80% drug compliance via pill counts and paper diaries. Changes will be calculated as post-treatment minus baseline values, with a negative value indicating a reduction in tumoral tryptophan metabolic rates resulting from kynurenine pathway inhibition. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference Between Dice Similarity Coefficients (DSC) of PET High Standardized Uptake Value (SUV) Tumor Volume and DSC of MRI-based Tumor Volume (d-PETsuv-MRI) in Arm 1 | From the time of the pre-radiotherapy scans (Baseline) up to tumor progression or study completion, assessed at a maximum follow-up of 2 years. | A comparative evaluation of the predictive accuracy of pre-radiotherapy imaging modalities (V1) in forecasting the spatial location of future tumor progression (V2) defined by RANO 2.0 criteria. For each participant, two separate Dice Similarity Coefficients (DSC) will be calculated against the final progression volume (V2): one using the pre-radiotherapy PET High SUV volume (V1\_PETsuv) and one using the structural MRI target volume (V1\_MRI). The primary endpoint (d-PETk-MRI) is the absolute difference calculated per patient as DSC\_PETsuv minus DSC\_MRI. The resulting continuous score ranges from -1 to +1. A positive score indicates that the novel kinetic PET parameter is a spatially superior predictor of subsequent localized tumor recurrence compared to standard clinical MRI planning fields. |
| Hazard Ratio for Progression-Free Survival Based on Pre-Radiotherapy (T1) [18F]FETrp PET High K Tumor Volume (PETk-T1) in Arm 1 | From date of initial diagnosis up to first documented RANO 2.0 disease progression, death, or study closure, assessed up to a maximum of 2 years. | Assessment of pre-radiotherapy metabolic tumor volume (PETk-T1, in cm³) as an independent prognostic predictor of progression-free survival (PFS). A multivariable Cox proportional hazards regression model will calculate the adjusted hazard ratio (HR) and 95% confidence interval for PFS per unit increase in PETk-T1 volume. The model will adjust for baseline clinical covariates. PFS is defined as time from the date of diagnosis to the first documented and verified disease progression (defined by the RANO 2.0 criteria9). Patients who are lost to follow-up or without disease progression at time of data cut off are censored at the time of last known disease progression follow-up. |
| Specificity of [18F]FETrp PET Kinetic Influx Rate (PETk) with a predefined L/C ratio threshold of 1.60 in differentiating Tumor Progression from Radiation Injury in Arm 2 | From the date of the [18F]FETrp PET/CT scan up to the date of confirmed ground truth designation via histopathology or serial MRI follow-up, assessed over a maximum period of 1 year per participant. | The diagnostic specificity of PETk post-radiation (T2) (PETk-T2) with a predefined L/C ratio threshold of 1.60 to correctly identify true glioblastoma progression. The true disease status (ground truth) is defined by follow-up serial MRIs using RANO 2.0 criteria or histopathologic evidence from surgical re-resection. Specificity is calculated as the proportion of true-negative cases (radiation injury) correctly identified by PETk out of all true-negative cases. |
| Positive Predictive Value (PPV) of [18F]FETrp PET K L/C Ratio for Glioblastoma Progression in Arm 2 | From the date of the [18F]FETrp PET/CT scan up to the date of confirmed ground truth designation via histopathology or serial MRI follow-up, assessed over a maximum period of 1 year per participant. | The proportion of participants with a positive \[18F\]FETrp PET K L/C ratio (≥ 1.60) who are confirmed to have true tumor progression via the composite ground truth reference standard (RANO 2.0 MRI follow-up or histopathology). |
| Negative Predictive Value (NPV) of [18F]FETrp PET K L/C Ratio for Glioblastoma Progression in Arm 2 | From the date of the [18F]FETrp PET/CT scan up to the date of confirmed ground truth designation via histopathology or serial MRI follow-up, assessed over a maximum period of 1 year per participant. | The proportion of participants with a negative \[18F\]FETrp PET K L/C ratio (\< 1.60) who are confirmed to have radiation-induced injury via the composite ground truth reference standard (RANO 2.0 MRI follow-up or histopathology). |
| Overall Diagnostic Accuracy of [18F]FETrp PET K L/C Ratio for Differentiating Tumor Progression From Radiation Injury in Arm 2 | From the date of the [18F]FETrp PET/CT scan up to the date of confirmed ground truth designation via histopathology or serial MRI follow-up, assessed over a maximum period of 1 year per participant. | The total proportion of correctly classified cases (true positives plus true negatives) using the \[18F\]FETrp PET K L/C ratio threshold of 1.60 divided by the total number of evaluable suspicious contrast-enhancing lesions. |
| Partial Area Under the Receiver Operating Characteristic Curve (pAUC) for [18F]FETrp PET K L/C Ratios in Arm 2 | From the date of the [18F]FETrp PET/CT scan up to the date of confirmed ground truth designation via histopathology or serial MRI follow-up, assessed over a maximum period of 1 year per participant. | The partial area under the receiver operating characteristic (ROC) curve generated by varying the continuous \[18F\]FETrp PET K L/C ratio values to assess overall classification performance across a clinically relevant range of specificities, utilizing the composite ground truth reference standard. |
| Change in [18F]FETrp PET Kinetic Influx Rate (K) Lesion-to-Contralateral (L/C) Ratios Following One Month of Standard of Care Plus IDO Inhibitor Treatment in Arm 3 | From Baseline (within 2 weeks prior to treatment initiation) to 1-month post-treatment (30 days ± 5 days, up to 44 days). | The change in the \[18F\]FETrp PET K-map lesion-to-contralateral (L/C) ratio from baseline to 1 month post-treatment. It is analyzed in the per-protocol population (at least 80% pill compliance and evaluable paired imaging). |
Countries
United States
Contacts
CONTACTCsaba Juhasz, M.D.,Ph.D.
PRINCIPAL_INVESTIGATORCsaba Juhasz, M.D.,Ph.D.
Wayne State University
Outcome results
None listed