Tryptophan-kynurenine Pathway PET Imaging in Human Gliomas
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 61
- 试验地点
- 1
- 主要终点
- 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
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
- •Exclusion Criteria:
- •Active connective tissue disorders, such as lupus or scleroderma.
- •History of allergic reaction to minocycline or any tetracyclines.
- •Ongoing treatment with warfarin with INR > 1.
- •History of colitis during antibiotics treatment.
结局指标
主要结局
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
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- 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.)
- 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.)
- 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.)
- 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.)
- 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.)
- 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.)
- 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.)
- 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).)
研究者
Csaba Juhasz
Principal Investigator
Barbara Ann Karmanos Cancer Institute