Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

MRI Scans in Evaluating the Effects of Radiation Therapy and Chemotherapy in Patients With Newly Diagnosed Glioblastoma Multiforme or Anaplastic Glioma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00756106
Recruitment Status : Terminated (Funding ended)
First Posted : September 19, 2008
Results First Posted : April 21, 2020
Last Update Posted : May 13, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Elizabeth R. Gerstner, MD, Massachusetts General Hospital

Tracking Information
First Submitted Date  ICMJE September 18, 2008
First Posted Date  ICMJE September 19, 2008
Results First Submitted Date  ICMJE March 23, 2020
Results First Posted Date  ICMJE April 21, 2020
Last Update Posted Date May 13, 2020
Study Start Date  ICMJE July 2008
Actual Primary Completion Date February 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 10, 2020)
  • Relative Cerebral Blood Volume as Measured by Perfusion-weighted MRI Before, During, and After Chemoradiotherapy [ Time Frame: Baseline, weekly during treatment, monthly following treatment for up to six months ]
    Relative cerebral blood volume (rCBV) is the blood volume in the region of interest (ROI) divided by the blood volume in the symmetrical region on the other side of the normal brain (control region). CBV was assessed using spin-echo post-contrast T1-weighted images. Multiple images were used to assess each participant at every time-point and the median value for each participant was calculated by time-point. The data presented represent the average of those median values at each time-point. The baseline value was measured twice (representing baseline 1 and 2) to make sure that the value was reproducible and to account for any variation attributable to measurement variation. CRT: Chemoradiotherapy Cx: The cycle number TMZ: temozolomide
  • Relative Cerebral Blood Flow as Measured by Perfusion-weighted MRI Before, During, and After Chemoradiotherapy [ Time Frame: Baseline, weekly during treatment, monthly following treatment for up to six months ]
    Relative cerebral blood flow (rCBF) is the blood flow rate (the volume of blood passing through the specified are over a specified period of time) in the region of interest (ROI) divided by the blood flow rate in the symmetrical region on the other side of the normal brain (control region). CBF was assessed using spin-echo post-contrast T1-weighted images. CBF was assessed using spin-echo post-contrast T1-weighted images. Multiple images were used to assess each participant at every time-point and the median value for each participant was calculated by time-point. The data presented represent the average of those median values at each time-point. The baseline value was measured twice (representing baseline 1 and 2) to make sure that the value was reproducible and to account for any variation attributable to measurement variation. CRT: Chemoradiotherapy Cx: The cycle number TMZ: temozolomide
  • Vessel Diameter as Measured by Perfusion-weighted MRI Before, During, and After Chemoradiotherapy [ Time Frame: Baseline, weekly during treatment, monthly following treatment for up to six months ]
  • Mean Transit Time as Measured by Perfusion-weighted MRI Before, During, and After Chemoradiotherapy [ Time Frame: Baseline, weekly during treatment, monthly following treatment for up to six months ]
    Mean transit time (MTT) corresponds to the average time, in seconds, that red blood cells spend within a determinate volume of capillary circulation.
  • Permeability-surface Area Product Before, During, and After Chemoradiotherapy [ Time Frame: Baseline, weekly during treatment, monthly following treatment for up to six months ]
    Permeability-surface Area Product (Ktrans). Ktrans reflects the efflux rate of contrast from blood plasma into the tissue extravascular extracellular space (EES). Ktrans was assessed using post-contrast T1-weighted images. Multiple images were used to assess each participant at every time-point and the median value for each participant was calculated by time-point. The data presented represent the average of those median values at each time-point. CRT: Chemoradiotherapy Cx: The cycle number TMZ: temozolomide
  • Apparent Diffusion Coefficient Before, During, and After Chemoradiotherapy [ Time Frame: Baseline, weekly during treatment, monthly following treatment for up to six months ]
    Apparent diffusion coefficient (ADC) is a measure of the magnitude of diffusion (of water molecules) within tissue. ADC was assessed using post-contrast T1-weighted images. Multiple images were used to assess each participant at every time-point and the median value for each participant was calculated by time-point. The data presented represent the average of those median values at each time-point. CRT: Chemoradiotherapy Cx: The cycle number TMZ: temozolomide
  • Tensor Fractional Anisotropy Before, During, and After Chemoradiotherapy [ Time Frame: Baseline, weekly during treatment, monthly following treatment for up to six months ]
    Fractional anisotropy (FA) is a measure of the directionality of the molecular motion of water.
  • Relative Regional Concentrations of Choline, N-acetyl-asparate, and Myoinositol as Measured by Magnetic Resonance Spectroscopy Before, During, and After Chemoradiotherapy to Interrogate Cell Membrane Turnover, Neuronal Integrity, and Glial Reactions [ Time Frame: Baseline, weekly during treatment, monthly following treatment for up to six months ]
  • Affects of a Short Period of 100% Oxygen Inhalation on Imaging of Tumor and Surrounding Tissue Regions of Interest, Specifically Cerebral Blood Volume Changes in Each Area as Compared to Room Air [ Time Frame: Baseline, weekly during treatment, monthly following treatment for up to six months ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 18, 2008)
  • Relative cerebral blood volume/flow, mean transit time, and mean vessel diameter as measured by perfusion-weighted MRI before, during, and after chemoradiotherapy
  • Permeability-surface Area Product Before, During, and After Chemoradiotherapy
  • Full water self-diffusion tensor before, during, and after chemoradiotherapy
  • Tensor Fractional Anisotropy Before, During, and After Chemoradiotherapy
  • Relative Regional Concentrations of Choline, N-acetyl-asparate, and Myoinositol as Measured by Magnetic Resonance Spectroscopy Before, During, and After Chemoradiotherapy to Interrogate Cell Membrane Turnover, Neuronal Integrity, and Glial Reactions
  • Affects of a Short Period of 100% Oxygen Inhalation on Imaging of Tumor and Surrounding Tissue Regions of Interest, Specifically Cerebral Blood Volume Changes in Each Area as Compared to Room Air
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: September 18, 2008)
  • Correlation between imaging changes, molecular markers, and clinical outcome
  • Correlation between blood and urine biomarkers and tumor expression of these markers
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE MRI Scans in Evaluating the Effects of Radiation Therapy and Chemotherapy in Patients With Newly Diagnosed Glioblastoma Multiforme or Anaplastic Glioma
Official Title  ICMJE Quantitative Assessment of the Early and Late Effects of Radiation and Chemotherapy on Glioblastoma Using Multiple MRI Techniques
Brief Summary

RATIONALE: Diagnostic procedures, such as MRI, may help in learning how well radiation therapy and chemotherapy work in killing tumor cells and allow doctors to plan better treatment.

PURPOSE: This clinical trial is studying MRI scans to see how well they evaluate the effects of radiation therapy and chemotherapy in patients with newly diagnosed glioblastoma multiforme or anaplastic glioma.

Detailed Description

OBJECTIVES:

Primary

  • To quantitatively compare the relative cerebral blood volume/flow, mean transit time, and mean vessel diameter as measured by perfusion-weighted MRI before, during, and after chemoradiotherapy in patients with newly diagnosed glioblastoma multiforme.
  • To measure the permeability-surface area product on a voxel-by-voxel basis before, during, and after chemoradiotherapy in these patients.
  • To measure the full water self-diffusion tensor on a voxel-by-voxel basis before, during, and after chemoradiotherapy in these patients.
  • To compare the tensor fractional anisotropy before, during, and after chemoradiotherapy in these patients.
  • To compare the relative regional concentrations of choline, N-acetyl-asparate, and myoinositol as measured by magnetic resonance spectroscopy before, during, and after chemoradiotherapy to interrogate cell membrane turnover, neuronal integrity, and glial reactions.
  • To test the affects of a short period of 100% oxygen inhalation on imaging of tumor and surrounding tissue regions of interest, specifically cerebral blood volume changes in each area as compared to room air.

Secondary

  • To collect blood and urine samples for correlation analysis between imaging changes, molecular markers (including genetic markers), and clinical outcome of glioblastoma multiforme (phenotypic information).
  • To correlate blood and urine biomarkers and blood genetic markers with tumor expression of these markers.

OUTLINE: Patients undergo radiotherapy once daily 5 days a week for 6 weeks. Patients also receive oral temozolomide once daily 7 days a week during radiotherapy. After completion of chemoradiotherapy, patients receive oral temozolomide once daily for 5 days. Treatment with temozolomide repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo MRI, including perfusion- and diffusion-weighted MRI, diffusion tensor imaging, and magnetic resonance spectroscopy prior to initiation of chemoradiotherapy, once weekly during chemoradiotherapy, and then monthly until tumor progression or until completion of 6 courses of post chemoradiotherapy.

After completion of study treatment, patients are followed annually.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE Brain and Central Nervous System Tumors
Intervention  ICMJE
  • Drug: temozolomide
    Temozolomide is administered according to standard of care practice guidelines. Dosing may be modified at the discretion of the treating investigator.
  • Other: Imaging biomarker analysis
    MRI
  • Radiation: Photon Radiation Therapy
    Radiation is administered to the tumor plus edema with a 1-2 centimeter margin for a total dose of 60 Gy in 30 fractions.
Study Arms  ICMJE Experimental: Temozolomide and Radiation Therapy
Interventions:
  • Drug: temozolomide
  • Other: Imaging biomarker analysis
  • Radiation: Photon Radiation Therapy
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: April 28, 2020)
15
Original Estimated Enrollment  ICMJE
 (submitted: September 18, 2008)
30
Actual Study Completion Date  ICMJE February 2012
Actual Primary Completion Date February 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Newly diagnosed anaplastic glioma (WHO grade III) or glioblastoma multiforme (WHO grade IV)
  • Measurable disease

    • Residual tumor size after surgery ≥ 1 cm in one dimension
  • Planning to undergo standard chemoradiotherapy with temozolomide

PATIENT CHARACTERISTICS:

  • Glomerular filtration rate ≥ 60 mL/min
  • Mini Mental Status Exam score > 15
  • Sufficiently competent to give informed consent
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier contraception during and for 2 months after completion of study treatment
  • No contraindication to MRI or to use of the contrast agent gadolinium, including any of the following:

    • Claustrophobia
    • Metallic objects or implanted medical devices (e.g., cardiac pacemaker, aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants)
    • Sickle cell disease
    • Renal failure
    • High risk for kidney disease (e.g., age > 60 years, diabetes, or history of systemic lupus erythematosus or multiple myeloma)
  • No known history of chronic obstructive pulmonary disease or emphysema
  • No other co-existing condition that, in the judgement of the investigator, may increase risk to the patient

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Non-VEGF investigational agent allowed
  • No concurrent chemotherapy (other than temozolomide)
  • No concurrent electron, proton, particle, or implant radiotherapy
  • No concurrent stereotactic radiosurgery
  • No concurrent anti-VEGF anti-tumor agents
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00756106
Other Study ID Numbers  ICMJE 07-292
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Elizabeth R. Gerstner, MD, Massachusetts General Hospital
Study Sponsor  ICMJE Massachusetts General Hospital
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Elizabeth Gerstner, MD Massachusetts General Hospital
PRS Account Massachusetts General Hospital
Verification Date April 2020

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