3T MRI Biomarkers of Glioma Treatment Response

Study Overview
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Brief Summary
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This pilot clinical trial studies advanced magnetic resonance imaging (MRI) techniques in measuring treatment response in patients with high-grade glioma. New diagnostic procedures, such as advanced MRI techniques at 3 Tesla, may be more effective than standard MRI in measuring treatment response in patients receiving treatment for high-grade gliomas.

Detailed Description
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PRIMARY OBJECTIVES: I. To correlate treatment-induced changes in quantitative MRI-based biomarkers-specifically, those sensitive to tumor protein content (amide proton transfer asymmetry [APTasym] from chemical exchange saturation transfer [CEST]), cellularity (apparent diffusion coefficient [ADC] from diffusion-weighted imaging [DWI]), and blood flow (volume transfer constant [K^trans] from dynamic contrast-enhanced [DCE]; cerebral blood flow [CBF] from dynamic susceptibility contrast [DSC])-with treatment-induced changes in tumor size, measured via standard anatomic MRI. II. To correlate treatment-induced changes in the above quantitative MRI endpoints with patient progression-free survival (PFS). OUTLINE: Patients undergo measurement of tumor protein content using CEST-MRI, cellularity using DWI-MRI, and blood flow using DCE-MRI and DSC-MRI within 2 weeks of treatment and at 2 and 4 weeks after initiation of treatment.

Official Title
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Early Detection of Glioma Treatment Response Using MRI-Based Biomarkers

Conditions
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Adult Anaplastic Astrocytoma, Adult Anaplastic Ependymoma, Adult Anaplastic Oligodendroglioma, Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Tumor

Intervention / Treatment
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* Device: 3-Tesla magnetic resonance imaging
* Device: CEST-MRI
* Device: DW-MRI
* Device: DCE-MRI
* Device: DSC-MRI
* Drug: IV administration of gadolinium-containing contrast agent


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must sign an institutional review board (IRB)-approved informed consent document Patients must have been diagnosed with high-grade glioma: World Health Organization (WHO) grade III: anaplastic astrocytoma, oligodendroglioma, ependymoma, or oligoastrocytoma; OR WHO grade IV: glioblastoma multiforme; or neuroepithelial tumors of uncertain origin (polar spongioblastoma, astroblastoma, or gliomatosis cerebri) As measured by conventional high spatial resolution MRI, the minimum diameter of the primary lesion (short axis) should be at least 5 mm Patients must be scheduled to receive: 1) standard chemotherapy with/without radiation therapy; OR 2) single-agent bevacizumab (Avastin) Exclusion Criteria: Patients with low-grade (WHO grade I or II) glioma Patients with metastatic disease Patients who have any type of bioimplant activated by mechanical, electronic, or magnetic means (e.g., cochlear implants, pacemakers, neurostimulators, biostimulators, electronic infusion pumps, etc), because such devices may be displaced or malfunction Patients who have any type of ferromagnetic bioimplant that could potentially be displaced Patients who have cerebral aneurysm clips Patients who may have shrapnel imbedded in their bodies (such as from war wounds), metal workers and machinists (potential for metallic fragments in or near the eyes) Patients with inadequate renal function (creatinine >= 1.5 times upper limit of normal) or acute or chronic renal insufficiency (glomerular filtration rate < 20 ml/min) Patients who are pregnant or breast feeding; urine pregnancy test will be performed on women of child bearing potential Patients who exhibit noticeable anxiety and/or claustrophobia or who exhibit severe vertigo when they are moved into the magnet bore Patients incapable of giving informed written consent, for the following reasons: Inability to adhere to the experimental protocols for any reason Inability to communicate with the research team Limited ability to give informed consent due to mental disability, altered mental status, confusion, cognitive impairment, or psychiatric disorders Patients scoring 14.5 or lower on the University of California at San Diego (UCSD) Brief Assessment of Consent Capacity (UBACC) Capacity to Consent Questionnaire will be excluded Prisoners or other individuals deemed to be susceptible to coercion For patients who have undergone surgical resection prior to joining the study, in whom baseline magnetic resonance (MR) images exhibit enough signal degradation (due to susceptibility artifact in the region of the surgical bed) such that the data are uninterpretable will be excluded

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 3-Tesla magnetic resonance imaging<br>Patients undergo 3-Tesla magnetic resonance imaging to measure tumor protein content (using CEST-MRI), cellularity (using DW-MRI), and blood flow (using DCE-MRI and DSC-MRI with IV administration of gadolinium-containing contrast agent) no more than 2 weeks before, and 2 and 4 weeks after, the initiation of treatment. | Device: 3-Tesla magnetic resonance imaging<br>* 3-Tesla MRI is a multiparametric imaging exam that includes MR pulse sequences for CEST-MRI, DW-MRI, DCE-MRI, and DSC-MRI<br>* Other names: 3T MRI;Device: CEST-MRI<br>* Undergo CEST-MRI<br>* Other names: chemical exchange saturation transfer MRI;Device: DW-MRI<br>* Undergo DWI-MRI<br>* Other names: diffusion-weighted MRI;Device: DCE-MRI<br>* Undergo DCE-MRI<br>* Other names: dynamic contrast-enhanced MRI;Device: DSC-MRI<br>* Undergo DSC-MRI<br>* Other names: dynamic susceptibility contrast MRI;Drug: IV administration of gadolinium-containing contrast agent<br>* Gadolinium-containing paramagnetic contrast agent (Magnevist®; Berlex Lab, Wayne, New Jersey) in delivered via intravenous (IV) infusion to achieve DCE and DSC contrast<br>* Other names: gadopentetate dimeglumine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Response | Number of patients in each response category, per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, summarized as follows for target lesion criteria: complete response (CR),disappearance of target lesions; partial response (PR), >=30% decrease in sum of longest diameter (LD) of target lesions; progressive disease (PD), >=20% increase in sum of LD of target lesions or appearance of new lesions; stable disease (SD), insufficient change in target lesions or new lesions to qualify as either PD or SD. Patients are categorized according to the best response achieved prior to occurrence of progressive disease, where best response hierarchy is CR>PR>SD>PD. | On-treatment date to date of disease progression (up to 12 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | Estimated probable duration of life without disease progression, from on-study date to earlier of progression date or date of death from any cause, using the Kaplan-Meier method with censoring. Disease progression is defined under RECIST v1.1 as >=20% increase in sum of longest diameters (LD) of target lesions, unequivocal progression of non-target lesions, or appearance of new lesions. | On-study date to lesser of date of progression or date of death from any cause (assessed at 6 months) |