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

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.


Condition or disease Intervention/treatment Phase
Brain and Central Nervous System Tumors Drug: temozolomide Other: Imaging biomarker analysis Radiation: Photon Radiation Therapy Not Applicable

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Quantitative Assessment of the Early and Late Effects of Radiation and Chemotherapy on Glioblastoma Using Multiple MRI Techniques
Study Start Date : July 2008
Actual Primary Completion Date : February 2012
Actual Study Completion Date : February 2012


Arm Intervention/treatment
Experimental: Temozolomide and Radiation Therapy 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.




Primary Outcome Measures :
  1. 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


  2. 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


  3. 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 ]
  4. 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.

  5. 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


  6. 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


  7. 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.

  8. 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 ]
  9. 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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00756106


Locations
Layout table for location information
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Elizabeth Gerstner, MD Massachusetts General Hospital
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Elizabeth R. Gerstner, MD, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00756106    
Other Study ID Numbers: 07-292
First Posted: September 19, 2008    Key Record Dates
Results First Posted: April 21, 2020
Last Update Posted: May 13, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Elizabeth R. Gerstner, MD, Massachusetts General Hospital:
adult glioblastoma
adult giant cell glioblastoma
adult gliosarcoma
adult anaplastic astrocytoma
adult anaplastic ependymoma
adult anaplastic oligodendroglioma
adult mixed glioma
Additional relevant MeSH terms:
Layout table for MeSH terms
Glioblastoma
Nervous System Neoplasms
Central Nervous System Neoplasms
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases
Temozolomide
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents