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

Brain and Central Nervous System Tumors Clinical Trial

Official title:

Quantitative Assessment of the Early and Late Effects of Radiation and Chemotherapy on Glioblastoma Using Multiple MRI Techniques

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00756106
• Other study ID #: 07-292
• Status: Terminated
• Phase: N/A
• Start date: July 2008
• Est. completion date: February 2012

Study information

• Verified date: April 2020
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 15
• Est. completion date: February 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Glioblastoma
• Nervous System Neoplasms

Intervention

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.

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relative Cerebral Blood Volume as Measured by Perfusion-weighted MRI Before, During, and After Chemoradiotherapy	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	Baseline, weekly during treatment, monthly following treatment for up to six months
Primary	Relative Cerebral Blood Flow as Measured by Perfusion-weighted MRI Before, During, and After Chemoradiotherapy	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	Baseline, weekly during treatment, monthly following treatment for up to six months
Primary	Vessel Diameter as Measured by Perfusion-weighted MRI Before, During, and After Chemoradiotherapy		Baseline, weekly during treatment, monthly following treatment for up to six months
Primary	Mean Transit Time as Measured by Perfusion-weighted MRI Before, During, and After Chemoradiotherapy	Mean transit time (MTT) corresponds to the average time, in seconds, that red blood cells spend within a determinate volume of capillary circulation.	Baseline, weekly during treatment, monthly following treatment for up to six months
Primary	Permeability-surface Area Product Before, During, and After Chemoradiotherapy	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	Baseline, weekly during treatment, monthly following treatment for up to six months
Primary	Apparent Diffusion Coefficient Before, During, and After Chemoradiotherapy	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	Baseline, weekly during treatment, monthly following treatment for up to six months
Primary	Tensor Fractional Anisotropy Before, During, and After Chemoradiotherapy	Fractional anisotropy (FA) is a measure of the directionality of the molecular motion of water.	Baseline, weekly during treatment, monthly following treatment for up to six months
Primary	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		Baseline, weekly during treatment, monthly following treatment for up to six months
Primary	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		Baseline, weekly during treatment, monthly following treatment for up to six months