3T MRI Biomarkers of Glioma Treatment Response

Early Phase 1

Terminated

• Conditions: Adult Anaplastic Ependymoma; Adult Gliosarcoma; Adult Anaplastic Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Anaplastic Oligodendroglioma; Recurrent Adult Brain Tumor
• Interventions: 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

• Registration Number: NCT01996527
• Lead Sponsor: Vanderbilt-Ingram Cancer Center

Brief Summary

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

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.

Study Timeline

• Study Start: 2012-05
• Study First Submitted: 2013-11-15
• Study First Submitted QC: 2013-11-26
• Study First Posted: 2013-11-27
• Primary Completion: 2015-11-23
• Study Completion: 2016-01-01
• Status Verified: 2017-04
• Last Update Submitted: 2017-04-13
• Last Update Posted: 2017-04-17

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 7

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
3-Tesla magnetic resonance imaging	CEST-MRI	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.
3-Tesla magnetic resonance imaging	3-Tesla magnetic resonance imaging	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.
3-Tesla magnetic resonance imaging	DW-MRI	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.
3-Tesla magnetic resonance imaging	DCE-MRI	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.
3-Tesla magnetic resonance imaging	IV administration of gadolinium-containing contrast agent	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.
3-Tesla magnetic resonance imaging	DSC-MRI	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.

Primary Outcome Measures

Name	Time	Method
Best Response	On-treatment date to date of disease progression (up to 12 weeks)	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.

Secondary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	On-study date to lesser of date of progression or date of death from any cause (assessed at 6 months)	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.

Trial Locations

Locations (1)

Vanderbilt-Ingram Cancer Center; 🇺🇸 Nashville, Tennessee, United States