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3T MRI Biomarkers of Glioma Treatment Response

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ClinicalTrials.gov Identifier: NCT01996527
Recruitment Status : Terminated (PI left institution)
First Posted : November 27, 2013
Last Update Posted : April 17, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Thomas Yankeelov, Vanderbilt-Ingram Cancer Center

November 15, 2013
November 27, 2013
April 17, 2017
May 2012
November 23, 2015   (Final data collection date for primary outcome measure)
Best Response [ Time Frame: 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.
Best Response [ Time Frame: On‐treatment date to date of disease progression (assess 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.
Complete list of historical versions of study NCT01996527 on ClinicalTrials.gov Archive Site
Progression Free Survival (PFS) [ Time Frame: 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.
Same as current
  • Changes in quantitative MRI-based biomarkers sensitive to tumor protein content [ Time Frame: Baseline to within 4 weeks after on-treatment date ]

    Evaluation of the following biological imaging metrics:

    1. Amide proton transfer asymmetry (APTasym, %) from CEST

  • Changes in quantitative MRI-based biomarkers sensitive to tumor cellularity and vascularity [ Time Frame: Baseline to within 4 weeks after on-treatment date ]

    Evaluation of the following biological imaging metrics:

    1. Apparent diffusion coefficient (ADC, mm2/s) from DW-MRI
    2. Tissue diffusion coefficient (Dt, mm2/s) from DW-MRI
    3. Pseudo-diffusion coefficient (Dp, mm2/s) from DW-MRI
  • Changes in quantitative MRI-based biomarkers sensitive to tumor perfusion and hemodynamics [ Time Frame: Baseline to within 4 weeks after on-treatment date ]

    Evaluation of the following biological imaging metrics:

    1. Volume transfer constant (Ktrans, 1/min) from DCE-MRI

  • Changes in quantitative MRI-based biomarkers sensitive to tumor perfusion and hemodynamics [ Time Frame: Baseline to within 4 weeks after on-treatment date ]

    Evaluation of the following biological imaging metrics:

    1. Perfusion fraction (fp, %) from DW-MRI
    2. Extravascular extracellular volume fraction (ve, %) from DCE-MRI
    3. Plasma volume fraction (vp, %) from DCE-MRI
    4. Cerebral blood volume (CBV, %) from DSC-MRI
  • Changes in quantitative MRI-based biomarkers sensitive to tumor perfusion and hemodynamics [ Time Frame: Baseline to within 4 weeks after on-treatment date ]

    Evaluation of the following biological imaging metrics:

    1. Cerebral blood flow (CBF, ml/min/100 g) from DSC-MRI

  • Changes in quantitative MRI-based biomarkers sensitive to tumor perfusion and hemodynamics [ Time Frame: Baseline to within 4 weeks after on-treatment date ]

    Evaluation of the following biological imaging metrics:

    1. Mean transit time (MTT, s) from DSC-MRI

  • Changes in quantitative MRI-based biomarkers sensitive to tumor protein content, tumor perfusion and hemodynamics [ Time Frame: Baseline to within 4 weeks after on-treatment date ]

    Evaluation of the following biological imaging metrics:

    1. Amide proton transfer asymmetry (APTasym) from CEST
    2. Apparent diffusion coefficient (ADC) from DW-MRI
    3. Volume transfer constant (Ktrans), extravascular extracellular volume fraction (ve), and plasma volume fraction (vp) from DCE-MRI
    4. Cerebral blood volume (CBV), cerebral blood flow (CBF) and mean transit time (MTT) from DSC-MRI Both conventional anatomic MRI and quantitative MRI sequences will be used in a single "hybrid" imaging exam to be conducted pre-treatment, early after treatment, and at a follow-up time point long
  • Changes in quantitative MRI-based biomarkers using 3.0 Tesla (3T) biomarkers [ Time Frame: Baseline to within 4 weeks after on-treatment date ]

    3T MRI techniques, that can supplement existing high-resolution anatomic imaging, will be performed to aid clinical decision-making for patients diagnosed with high-grade glioma. These techniques include:

    1. Chemical Exchange Saturation Transfer (CEST)4
    2. Diffusion Weighted MRI (DWI, or DW-MRI)5,6
    3. Dynamic Contrast Enhanced MRI (DCE-MRI)7
    4. Dynamic Susceptibility Contrast MRI (DSC-MRI)8
 
3T MRI Biomarkers of Glioma Treatment Response
Early Detection of Glioma Treatment Response Using MRI-Based Biomarkers
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.

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.

Interventional
Early Phase 1
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
  • Adult Anaplastic Astrocytoma
  • Adult Anaplastic Ependymoma
  • Adult Anaplastic Oligodendroglioma
  • Adult Giant Cell Glioblastoma
  • Adult Glioblastoma
  • Adult Gliosarcoma
  • Recurrent Adult Brain Tumor
  • Device: 3-Tesla magnetic resonance imaging
    3-Tesla MRI is a multiparametric imaging exam that includes MR pulse sequences for CEST-MRI, DW-MRI, DCE-MRI, and DSC-MRI
    Other Names:
    • 3-Tesla MRI
    • 3T MRI
  • Device: CEST-MRI
    Undergo CEST-MRI
    Other Name: chemical exchange saturation transfer MRI
  • Device: DW-MRI
    Undergo DWI-MRI
    Other Name: diffusion-weighted MRI
  • Device: DCE-MRI
    Undergo DCE-MRI
    Other Name: dynamic contrast-enhanced MRI
  • Device: DSC-MRI
    Undergo DSC-MRI
    Other Name: dynamic susceptibility contrast MRI
  • Drug: IV administration of gadolinium-containing contrast agent
    Gadolinium-containing paramagnetic contrast agent (Magnevist®; Berlex Lab, Wayne, New Jersey) in delivered via intravenous (IV) infusion to achieve DCE and DSC contrast
    Other Names:
    • Magnevist®
    • gadopentetate dimeglumine
Experimental: 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.
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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
7
22
January 1, 2016
November 23, 2015   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01996527
VICC NEU 1268
NCI-2013-02195 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
P30CA068485 ( U.S. NIH Grant/Contract )
Yes
Not Provided
Not Provided
Thomas Yankeelov, Vanderbilt-Ingram Cancer Center
Vanderbilt-Ingram Cancer Center
National Cancer Institute (NCI)
Principal Investigator: Chad Quarles Vanderbilt-Ingram Cancer Center
Vanderbilt-Ingram Cancer Center
April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP